US20100056615A1 - Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders - Google Patents
Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders Download PDFInfo
- Publication number
- US20100056615A1 US20100056615A1 US12/515,329 US51532907A US2010056615A1 US 20100056615 A1 US20100056615 A1 US 20100056615A1 US 51532907 A US51532907 A US 51532907A US 2010056615 A1 US2010056615 A1 US 2010056615A1
- Authority
- US
- United States
- Prior art keywords
- treatment
- formulae
- weight
- prevention
- tricyclic diterpene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229930004069 diterpene Natural products 0.000 title claims abstract description 79
- 238000011282 treatment Methods 0.000 title claims abstract description 56
- 230000002265 prevention Effects 0.000 title claims abstract description 43
- 238000011278 co-treatment Methods 0.000 title claims abstract description 37
- 208000027866 inflammatory disease Diseases 0.000 title claims abstract description 33
- 208000012659 Joint disease Diseases 0.000 title claims abstract description 25
- 125000000567 diterpene group Chemical group 0.000 title abstract description 27
- 239000002417 nutraceutical Substances 0.000 claims abstract description 29
- 235000021436 nutraceutical agent Nutrition 0.000 claims abstract description 29
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims description 81
- 150000004141 diterpene derivatives Chemical class 0.000 claims description 52
- 235000013305 food Nutrition 0.000 claims description 44
- 235000015872 dietary supplement Nutrition 0.000 claims description 38
- -1 C3-5-acyloxy Chemical group 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 29
- 239000002537 cosmetic Substances 0.000 claims description 28
- NPQAMUFQEFLLCY-UHFFFAOYSA-N Sageone Chemical compound C1=2C(O)=C(O)C(C(C)C)=CC=2CCC2=C1C(=O)CCC2(C)C NPQAMUFQEFLLCY-UHFFFAOYSA-N 0.000 claims description 27
- 201000004624 Dermatitis Diseases 0.000 claims description 23
- QQNSARJGBPMQDI-UHFFFAOYSA-N carnosic acid 12-methyl ether Natural products CC1(C)CCCC2(C(O)=O)C(C(O)=C(C(=C3)C(C)C)OC)=C3CCC21 QQNSARJGBPMQDI-UHFFFAOYSA-N 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- RCVGXYUBWJMZTF-MGPUTAFESA-N sageone Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C=O)C1=C2C=C(C(C)C)C(O)=C1O RCVGXYUBWJMZTF-MGPUTAFESA-N 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 18
- 206010003246 arthritis Diseases 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 16
- ZBPGOZPDUZTLRB-MGPUTAFESA-N 11,20-dihydroxyferruginol Chemical compound CC([C@@H]1CC2)(C)CCC[C@]1(CO)C1=C2C=C(C(C)C)C(O)=C1O ZBPGOZPDUZTLRB-MGPUTAFESA-N 0.000 claims description 15
- 206010042496 Sunburn Diseases 0.000 claims description 14
- ZBPGOZPDUZTLRB-UHFFFAOYSA-N abietatriene triol Natural products C1CC2C(C)(C)CCCC2(CO)C2=C1C=C(C(C)C)C(O)=C2O ZBPGOZPDUZTLRB-UHFFFAOYSA-N 0.000 claims description 14
- MSWJSDLNPCSSNW-MISYRCLQSA-N (1r,4as,10ar)-1,4a-dimethyl-9-oxo-7-propan-2-yl-3,4,10,10a-tetrahydro-2h-phenanthrene-1-carboxylic acid Chemical compound OC(=O)[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3C(=O)C[C@H]21 MSWJSDLNPCSSNW-MISYRCLQSA-N 0.000 claims description 13
- ZRVDANDJSTYELM-UHFFFAOYSA-N trans-totarol Natural products C1CC2C(C)(C)CCCC2(C)C2=C1C(C(C)C)=C(O)C=C2 ZRVDANDJSTYELM-UHFFFAOYSA-N 0.000 claims description 13
- 210000000845 cartilage Anatomy 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- QXNWVJOHUAQHLM-AZUAARDMSA-N ferruginol Chemical compound CC([C@@H]1CC2)(C)CCC[C@]1(C)C1=C2C=C(C(C)C)C(O)=C1 QXNWVJOHUAQHLM-AZUAARDMSA-N 0.000 claims description 12
- ZRVDANDJSTYELM-FXAWDEMLSA-N totarol Chemical compound CC([C@@H]1CC2)(C)CCC[C@]1(C)C1=C2C(C(C)C)=C(O)C=C1 ZRVDANDJSTYELM-FXAWDEMLSA-N 0.000 claims description 12
- 229940074347 totarol Drugs 0.000 claims description 12
- NFEAIVZJRVEKFD-UHFFFAOYSA-N Hydroxytotarol Natural products C1CC2C(C)(CO)CCCC2(C)C2=C1C(C(C)C)=C(O)C=C2 NFEAIVZJRVEKFD-UHFFFAOYSA-N 0.000 claims description 11
- CKZZREIPBTYJEQ-UHFFFAOYSA-N Totarol Natural products C1CC2C(C)(C)CCCC2(C)C2=C1C(C(C)C)=C(C)C=C2 CKZZREIPBTYJEQ-UHFFFAOYSA-N 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- HOJWCCXHGGCJQV-YLJYHZDGSA-N ferruginol Natural products CC(C)c1ccc2c(CC[C@@H]3C(C)(C)CCC[C@]23C)c1O HOJWCCXHGGCJQV-YLJYHZDGSA-N 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
- ISECDNAMJMNAHZ-UHFFFAOYSA-N 7-Oxodehydroabietic acid Natural products OC(=O)C1(C)CCCC2(C)C3=CC=C(C(C)C)C=C3CC(=O)C21 ISECDNAMJMNAHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000000419 plant extract Substances 0.000 claims description 9
- TWZMQZBMHUHORI-UHFFFAOYSA-N royleanonic acid Natural products CC(C)C1=C(O)C(=O)C2=C(CCC3C(C)(C)CCCC23C(=O)O)C1=O TWZMQZBMHUHORI-UHFFFAOYSA-N 0.000 claims description 9
- 239000013589 supplement Substances 0.000 claims description 9
- 230000001684 chronic effect Effects 0.000 claims description 8
- 238000012423 maintenance Methods 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- XNPVHIQPSAZTLC-UHFFFAOYSA-N 7-Methylrosmanol Chemical compound C12=C(O)C(O)=C(C(C)C)C=C2C(OC)C2C3C(C)(C)CCCC31C(=O)O2 XNPVHIQPSAZTLC-UHFFFAOYSA-N 0.000 claims description 6
- 230000008355 cartilage degradation Effects 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- WAEGSBQAQLUGKP-UHFFFAOYSA-N methylrosmanol Natural products COC1C2OC(=O)C3(CCCC(C)(C)C23)c4c(OC(=O)C)c(OC(=O)C)c(cc14)C(C)C WAEGSBQAQLUGKP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 230000037231 joint health Effects 0.000 claims description 2
- 206010007710 Cartilage injury Diseases 0.000 claims 1
- 230000003848 cartilage regeneration Effects 0.000 claims 1
- 241000196324 Embryophyta Species 0.000 description 52
- 239000000284 extract Substances 0.000 description 46
- 239000000463 material Substances 0.000 description 43
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 39
- 210000003491 skin Anatomy 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000004615 ingredient Substances 0.000 description 28
- 238000003756 stirring Methods 0.000 description 20
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 230000014509 gene expression Effects 0.000 description 18
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 18
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 17
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical class CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 17
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 17
- 229960001679 octinoxate Drugs 0.000 description 17
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 16
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 16
- 201000008482 osteoarthritis Diseases 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- 230000002757 inflammatory effect Effects 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- OSCJHTSDLYVCQC-UHFFFAOYSA-N 2-ethylhexyl 4-[[4-[4-(tert-butylcarbamoyl)anilino]-6-[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)NC(C)(C)C)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 OSCJHTSDLYVCQC-UHFFFAOYSA-N 0.000 description 14
- 241000282412 Homo Species 0.000 description 14
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 230000004054 inflammatory process Effects 0.000 description 14
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 13
- 206010061218 Inflammation Diseases 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- DLAHAXOYRFRPFQ-UHFFFAOYSA-N dodecyl benzoate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC=CC=C1 DLAHAXOYRFRPFQ-UHFFFAOYSA-N 0.000 description 12
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 239000002245 particle Substances 0.000 description 12
- 239000002304 perfume Substances 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- XLOMVQKBTHCTTD-UHFFFAOYSA-N zinc oxide Inorganic materials [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 12
- 229920002125 Sokalan® Polymers 0.000 description 11
- 206010000496 acne Diseases 0.000 description 11
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 206010039073 rheumatoid arthritis Diseases 0.000 description 11
- HEOCBCNFKCOKBX-RELGSGGGSA-N (1s,2e,4r)-4,7,7-trimethyl-2-[(4-methylphenyl)methylidene]bicyclo[2.2.1]heptan-3-one Chemical compound C1=CC(C)=CC=C1\C=C/1C(=O)[C@]2(C)CC[C@H]\1C2(C)C HEOCBCNFKCOKBX-RELGSGGGSA-N 0.000 description 10
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 10
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 10
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 10
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 235000016709 nutrition Nutrition 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- NFEAIVZJRVEKFD-DFQSSKMNSA-N (4bs,8s,8ar)-8-(hydroxymethyl)-4b,8-dimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-ol Chemical compound OC[C@](C)([C@@H]1CC2)CCC[C@]1(C)C1=C2C(C(C)C)=C(O)C=C1 NFEAIVZJRVEKFD-DFQSSKMNSA-N 0.000 description 9
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 9
- 208000002874 Acne Vulgaris Diseases 0.000 description 9
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 9
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 238000013019 agitation Methods 0.000 description 9
- 235000013361 beverage Nutrition 0.000 description 9
- 229940067596 butylparaben Drugs 0.000 description 9
- 150000001720 carbohydrates Chemical class 0.000 description 9
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 9
- 235000005911 diet Nutrition 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 9
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 9
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 9
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 9
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 9
- 239000000796 flavoring agent Substances 0.000 description 9
- 210000001503 joint Anatomy 0.000 description 9
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 9
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 9
- 229960002216 methylparaben Drugs 0.000 description 9
- 229960005323 phenoxyethanol Drugs 0.000 description 9
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 9
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 9
- 229960003415 propylparaben Drugs 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 229940042585 tocopherol acetate Drugs 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 8
- 235000013734 beta-carotene Nutrition 0.000 description 8
- 239000011648 beta-carotene Substances 0.000 description 8
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 8
- 229960002747 betacarotene Drugs 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 235000014633 carbohydrates Nutrition 0.000 description 8
- 239000003995 emulsifying agent Substances 0.000 description 8
- FOYKKGHVWRFIBD-UHFFFAOYSA-N gamma-tocopherol acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 FOYKKGHVWRFIBD-UHFFFAOYSA-N 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 235000013336 milk Nutrition 0.000 description 8
- 239000008267 milk Substances 0.000 description 8
- 210000004080 milk Anatomy 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000012216 screening Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 8
- XNEFYCZVKIDDMS-UHFFFAOYSA-N avobenzone Chemical compound C1=CC(OC)=CC=C1C(=O)CC(=O)C1=CC=C(C(C)(C)C)C=C1 XNEFYCZVKIDDMS-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 235000019634 flavors Nutrition 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000003755 preservative agent Substances 0.000 description 7
- 229940088594 vitamin Drugs 0.000 description 7
- 229930003231 vitamin Natural products 0.000 description 7
- 235000013343 vitamin Nutrition 0.000 description 7
- 239000011782 vitamin Substances 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- LFNJOAMWXNMXHJ-FKIZINRSSA-N (4ar,10as)-8-hydroxy-1,1-dimethyl-5,6-dioxo-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-4a-carboxylic acid Chemical compound C([C@@]12C(O)=O)CCC(C)(C)[C@@H]1CCC1=C2C(=O)C(=O)C(C(C)C)=C1O LFNJOAMWXNMXHJ-FKIZINRSSA-N 0.000 description 6
- JGUMTYWKIBJSTN-UHFFFAOYSA-N 2-ethylhexyl 4-[[4,6-bis[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 JGUMTYWKIBJSTN-UHFFFAOYSA-N 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 6
- 108010035532 Collagen Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 6
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 6
- 201000004681 Psoriasis Diseases 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 229960001631 carbomer Drugs 0.000 description 6
- 229960000541 cetyl alcohol Drugs 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000037213 diet Effects 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- 235000015112 vegetable and seed oil Nutrition 0.000 description 6
- HIPQTCQUXOFTFI-UHFFFAOYSA-N 2-methoxy-1,3-diphenylpropane-1,3-dione Chemical compound C=1C=CC=CC=1C(=O)C(OC)C(=O)C1=CC=CC=C1 HIPQTCQUXOFTFI-UHFFFAOYSA-N 0.000 description 5
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 5
- FMRHJJZUHUTGKE-UHFFFAOYSA-N Ethylhexyl salicylate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1O FMRHJJZUHUTGKE-UHFFFAOYSA-N 0.000 description 5
- 244000299461 Theobroma cacao Species 0.000 description 5
- 102000007544 Whey Proteins Human genes 0.000 description 5
- 108010046377 Whey Proteins Proteins 0.000 description 5
- 229960000458 allantoin Drugs 0.000 description 5
- UPOYFZYFGWBUKL-UHFFFAOYSA-N amiphenazole Chemical compound S1C(N)=NC(N)=C1C1=CC=CC=C1 UPOYFZYFGWBUKL-UHFFFAOYSA-N 0.000 description 5
- 229950001798 amiphenazole Drugs 0.000 description 5
- 235000010323 ascorbic acid Nutrition 0.000 description 5
- 239000011668 ascorbic acid Substances 0.000 description 5
- 229960005070 ascorbic acid Drugs 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 208000037976 chronic inflammation Diseases 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 229960004697 enzacamene Drugs 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 229940100498 polysilicone-15 Drugs 0.000 description 5
- 229920002282 polysilicones-15 Polymers 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- OJTDGPLHRSZIAV-UHFFFAOYSA-N propane-1,2-diol Chemical compound CC(O)CO.CC(O)CO OJTDGPLHRSZIAV-UHFFFAOYSA-N 0.000 description 5
- 235000014214 soft drink Nutrition 0.000 description 5
- 239000008279 sol Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 239000008158 vegetable oil Substances 0.000 description 5
- QQNSARJGBPMQDI-YCRPNKLZSA-N (4ar,10as)-5-hydroxy-6-methoxy-1,1-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-4a-carboxylic acid Chemical compound CC1(C)CCC[C@]2(C(O)=O)C(C(O)=C(C(=C3)C(C)C)OC)=C3CC[C@H]21 QQNSARJGBPMQDI-YCRPNKLZSA-N 0.000 description 4
- 244000215068 Acacia senegal Species 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 206010012438 Dermatitis atopic Diseases 0.000 description 4
- 206010012442 Dermatitis contact Diseases 0.000 description 4
- XTJFFFGAUHQWII-UHFFFAOYSA-N Dibutyl adipate Chemical compound CCCCOC(=O)CCCCC(=O)OCCCC XTJFFFGAUHQWII-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 229920000084 Gum arabic Polymers 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 201000009053 Neurodermatitis Diseases 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 4
- 241001303601 Rosacea Species 0.000 description 4
- 206010039792 Seborrhoea Diseases 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 206010053615 Thermal burn Diseases 0.000 description 4
- 229930003427 Vitamin E Natural products 0.000 description 4
- 206010048222 Xerosis Diseases 0.000 description 4
- 0 [1*]C1=C2C(=C([4*])C([3*])=C1[2*])C1([5*])C([11*])([12*])CCC([7*])([8*])C1([6*])C([10*])C2[9*].[2*]C1=C([3*])C(=O)C2=C(C1=O)C([9*])CC1([6*])C([7*])([8*])CCCC21[13*] Chemical compound [1*]C1=C2C(=C([4*])C([3*])=C1[2*])C1([5*])C([11*])([12*])CCC([7*])([8*])C1([6*])C([10*])C2[9*].[2*]C1=C([3*])C(=O)C2=C(C1=O)C([9*])CC1([6*])C([7*])([8*])CCCC21[13*] 0.000 description 4
- 235000010489 acacia gum Nutrition 0.000 description 4
- 239000000205 acacia gum Substances 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 201000008937 atopic dermatitis Diseases 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- XVAMCHGMPYWHNL-UHFFFAOYSA-N bemotrizinol Chemical compound OC1=CC(OCC(CC)CCCC)=CC=C1C1=NC(C=2C=CC(OC)=CC=2)=NC(C=2C(=CC(OCC(CC)CCCC)=CC=2)O)=N1 XVAMCHGMPYWHNL-UHFFFAOYSA-N 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 235000019219 chocolate Nutrition 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 208000010247 contact dermatitis Diseases 0.000 description 4
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229940029985 mineral supplement Drugs 0.000 description 4
- 235000020786 mineral supplement Nutrition 0.000 description 4
- 235000020772 multivitamin supplement Nutrition 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
- FMJSMJQBSVNSBF-UHFFFAOYSA-N octocrylene Chemical compound C=1C=CC=CC=1C(=C(C#N)C(=O)OCC(CC)CCCC)C1=CC=CC=C1 FMJSMJQBSVNSBF-UHFFFAOYSA-N 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 239000000049 pigment Substances 0.000 description 4
- 229920001296 polysiloxane Polymers 0.000 description 4
- RMGVATURDVPNOZ-UHFFFAOYSA-M potassium;hexadecyl hydrogen phosphate Chemical compound [K+].CCCCCCCCCCCCCCCCOP(O)([O-])=O RMGVATURDVPNOZ-UHFFFAOYSA-M 0.000 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 230000004224 protection Effects 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 201000004700 rosacea Diseases 0.000 description 4
- 235000002020 sage Nutrition 0.000 description 4
- 208000008742 seborrheic dermatitis Diseases 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 239000011709 vitamin E Substances 0.000 description 4
- 229940046009 vitamin E Drugs 0.000 description 4
- 235000019165 vitamin E Nutrition 0.000 description 4
- 239000011787 zinc oxide Substances 0.000 description 4
- DBSABEYSGXPBTA-RXSVEWSESA-N (2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;phosphoric acid Chemical class OP(O)(O)=O.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O DBSABEYSGXPBTA-RXSVEWSESA-N 0.000 description 3
- OIQXFRANQVWXJF-QBFSEMIESA-N (2z)-2-benzylidene-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound CC1(C)C2CCC1(C)C(=O)\C2=C/C1=CC=CC=C1 OIQXFRANQVWXJF-QBFSEMIESA-N 0.000 description 3
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical class C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 3
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical class NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 3
- 108010067219 Aggrecans Proteins 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108010074051 C-Reactive Protein Proteins 0.000 description 3
- 102100032752 C-reactive protein Human genes 0.000 description 3
- 102000012422 Collagen Type I Human genes 0.000 description 3
- 108010022452 Collagen Type I Proteins 0.000 description 3
- 102100027995 Collagenase 3 Human genes 0.000 description 3
- 108050005238 Collagenase 3 Proteins 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229920002774 Maltodextrin Polymers 0.000 description 3
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 3
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 description 3
- 208000001132 Osteoporosis Diseases 0.000 description 3
- 241000218689 Podocarpus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 102100030416 Stromelysin-1 Human genes 0.000 description 3
- 101710108790 Stromelysin-1 Proteins 0.000 description 3
- 235000009499 Vanilla fragrans Nutrition 0.000 description 3
- 244000263375 Vanilla tahitensis Species 0.000 description 3
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 3
- 229920001938 Vegetable gum Polymers 0.000 description 3
- 229930003268 Vitamin C Natural products 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 229960004101 bemotrizinol Drugs 0.000 description 3
- 229960004217 benzyl alcohol Drugs 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 3
- 108010033929 calcium caseinate Proteins 0.000 description 3
- 229940071162 caseinate Drugs 0.000 description 3
- 230000001925 catabolic effect Effects 0.000 description 3
- 229940081733 cetearyl alcohol Drugs 0.000 description 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 235000014510 cooky Nutrition 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- NZZIMKJIVMHWJC-UHFFFAOYSA-N dibenzoylmethane Chemical class C=1C=CC=CC=1C(=O)CC(=O)C1=CC=CC=C1 NZZIMKJIVMHWJC-UHFFFAOYSA-N 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- FDATWRLUYRHCJE-UHFFFAOYSA-N diethylamino hydroxybenzoyl hexyl benzoate Chemical compound CCCCCCOC(=O)C1=CC=CC=C1C(=O)C1=CC=C(N(CC)CC)C=C1O FDATWRLUYRHCJE-UHFFFAOYSA-N 0.000 description 3
- 229940008099 dimethicone Drugs 0.000 description 3
- 239000004205 dimethyl polysiloxane Substances 0.000 description 3
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 3
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 3
- 230000006806 disease prevention Effects 0.000 description 3
- GLCJMPWWQKKJQZ-UHFFFAOYSA-L disodium;2-[4-(4,6-disulfonato-1h-benzimidazol-2-yl)phenyl]-1h-benzimidazole-4,6-disulfonate;hydron Chemical compound [Na+].[Na+].C1=C(S(O)(=O)=O)C=C2NC(C3=CC=C(C=C3)C3=NC4=C(C=C(C=C4N3)S(=O)(=O)O)S([O-])(=O)=O)=NC2=C1S([O-])(=O)=O GLCJMPWWQKKJQZ-UHFFFAOYSA-L 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 235000013312 flour Nutrition 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 208000019622 heart disease Diseases 0.000 description 3
- 229940049290 hydrogenated coco-glycerides Drugs 0.000 description 3
- 150000002484 inorganic compounds Chemical class 0.000 description 3
- 229910010272 inorganic material Inorganic materials 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- NJTGANWAUPEOAX-UHFFFAOYSA-N molport-023-220-454 Chemical compound OCC(O)CO.OCC(O)CO NJTGANWAUPEOAX-UHFFFAOYSA-N 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 229940101267 panthenol Drugs 0.000 description 3
- 235000020957 pantothenol Nutrition 0.000 description 3
- 239000011619 pantothenol Substances 0.000 description 3
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 235000014438 salad dressings Nutrition 0.000 description 3
- 230000037307 sensitive skin Effects 0.000 description 3
- 235000011888 snacks Nutrition 0.000 description 3
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 3
- 239000004299 sodium benzoate Substances 0.000 description 3
- 235000010234 sodium benzoate Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000000475 sunscreen effect Effects 0.000 description 3
- 239000000516 sunscreening agent Substances 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 3
- 229910052721 tungsten Inorganic materials 0.000 description 3
- 235000019154 vitamin C Nutrition 0.000 description 3
- 239000011718 vitamin C Substances 0.000 description 3
- 239000000341 volatile oil Substances 0.000 description 3
- 235000021119 whey protein Nutrition 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 2
- QMIBDVOQOZDSEN-UHFFFAOYSA-N 2-phenylbenzimidazole-2-sulfonic acid Chemical compound N1=C2C=CC=CC2=NC1(S(=O)(=O)O)C1=CC=CC=C1 QMIBDVOQOZDSEN-UHFFFAOYSA-N 0.000 description 2
- PMYDPQQPEAYXKD-UHFFFAOYSA-N 3-hydroxy-n-naphthalen-2-ylnaphthalene-2-carboxamide Chemical compound C1=CC=CC2=CC(NC(=O)C3=CC4=CC=CC=C4C=C3O)=CC=C21 PMYDPQQPEAYXKD-UHFFFAOYSA-N 0.000 description 2
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 2
- 102000016284 Aggrecans Human genes 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- ZCTQGTTXIYCGGC-UHFFFAOYSA-N Benzyl salicylate Chemical compound OC1=CC=CC=C1C(=O)OCC1=CC=CC=C1 ZCTQGTTXIYCGGC-UHFFFAOYSA-N 0.000 description 2
- 239000004135 Bone phosphate Substances 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000195940 Bryophyta Species 0.000 description 2
- 229910021555 Chromium Chloride Inorganic materials 0.000 description 2
- 241000723346 Cinnamomum camphora Species 0.000 description 2
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical compound [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 2
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 235000021559 Fruit Juice Concentrate Nutrition 0.000 description 2
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 241000721662 Juniperus Species 0.000 description 2
- 229920001732 Lignosulfonate Polymers 0.000 description 2
- 239000005913 Maltodextrin Substances 0.000 description 2
- ABSPRNADVQNDOU-UHFFFAOYSA-N Menaquinone 1 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(C)C(=O)C2=C1 ABSPRNADVQNDOU-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 108010003541 Platelet Activating Factor Proteins 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 206010063562 Radiation skin injury Diseases 0.000 description 2
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical class CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 2
- 244000178231 Rosmarinus officinalis Species 0.000 description 2
- 241000282849 Ruminantia Species 0.000 description 2
- 244000261549 Salvia sp Species 0.000 description 2
- 235000010151 Salvia sp Nutrition 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 239000004904 UV filter Substances 0.000 description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 description 2
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 150000001343 alkyl silanes Chemical class 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 2
- 229940063655 aluminum stearate Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000001195 anabolic effect Effects 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000036778 atheroma formation Effects 0.000 description 2
- 230000003796 beauty Effects 0.000 description 2
- JAEJSNFTJMYIEF-UHFFFAOYSA-L benzylmalonate group Chemical group C(C1=CC=CC=C1)C(C(=O)[O-])C(=O)[O-] JAEJSNFTJMYIEF-UHFFFAOYSA-L 0.000 description 2
- 235000015895 biscuits Nutrition 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 2
- 235000011092 calcium acetate Nutrition 0.000 description 2
- 239000001639 calcium acetate Substances 0.000 description 2
- 229960005147 calcium acetate Drugs 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 229960002079 calcium pantothenate Drugs 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229960000846 camphor Drugs 0.000 description 2
- 229930008380 camphor Natural products 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 229920002678 cellulose Chemical class 0.000 description 2
- 239000001913 cellulose Chemical class 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 235000013351 cheese Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical class COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 229940108925 copper gluconate Drugs 0.000 description 2
- 229910000365 copper sulfate Inorganic materials 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 229960002104 cyanocobalamin Drugs 0.000 description 2
- 235000000639 cyanocobalamin Nutrition 0.000 description 2
- 239000011666 cyanocobalamin Substances 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 229940100539 dibutyl adipate Drugs 0.000 description 2
- 229940031578 diisopropyl adipate Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- HUVYTMDMDZRHBN-UHFFFAOYSA-N drometrizole trisiloxane Chemical compound C[Si](C)(C)O[Si](C)(O[Si](C)(C)C)CC(C)CC1=CC(C)=CC(N2N=C3C=CC=CC3=N2)=C1O HUVYTMDMDZRHBN-UHFFFAOYSA-N 0.000 description 2
- 150000002066 eicosanoids Chemical class 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 235000020774 essential nutrients Nutrition 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- ZUVCYFMOHFTGDM-UHFFFAOYSA-N hexadecyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(O)=O ZUVCYFMOHFTGDM-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 229940060367 inert ingredients Drugs 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 229960000367 inositol Drugs 0.000 description 2
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 2
- WBJZTOZJJYAKHQ-UHFFFAOYSA-K iron(3+) phosphate Chemical compound [Fe+3].[O-]P([O-])([O-])=O WBJZTOZJJYAKHQ-UHFFFAOYSA-K 0.000 description 2
- 229910000399 iron(III) phosphate Inorganic materials 0.000 description 2
- 208000018937 joint inflammation Diseases 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 235000021056 liquid food Nutrition 0.000 description 2
- 239000000395 magnesium oxide Substances 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical class [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 2
- 229940035034 maltodextrin Drugs 0.000 description 2
- 208000011661 metabolic syndrome X Diseases 0.000 description 2
- 229910044991 metal oxide Inorganic materials 0.000 description 2
- 150000004706 metal oxides Chemical class 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000004200 microcrystalline wax Substances 0.000 description 2
- 235000019808 microcrystalline wax Nutrition 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- 235000011929 mousse Nutrition 0.000 description 2
- 229960003966 nicotinamide Drugs 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 235000019520 non-alcoholic beverage Nutrition 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 229960000601 octocrylene Drugs 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000007968 orange flavor Substances 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 125000005375 organosiloxane group Chemical group 0.000 description 2
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical class [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 description 2
- 235000021485 packed food Nutrition 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 235000021400 peanut butter Nutrition 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 description 2
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 2
- 235000019175 phylloquinone Nutrition 0.000 description 2
- 239000011772 phylloquinone Substances 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 229960001898 phytomenadione Drugs 0.000 description 2
- 229920001515 polyalkylene glycol Polymers 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Substances [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 235000011962 puddings Nutrition 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 2
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 2
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 235000019192 riboflavin Nutrition 0.000 description 2
- 239000002151 riboflavin Substances 0.000 description 2
- 229960002477 riboflavin Drugs 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 235000015067 sauces Nutrition 0.000 description 2
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 239000011684 sodium molybdate Substances 0.000 description 2
- 235000015393 sodium molybdate Nutrition 0.000 description 2
- TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000011655 sodium selenate Substances 0.000 description 2
- 235000018716 sodium selenate Nutrition 0.000 description 2
- 229960001881 sodium selenate Drugs 0.000 description 2
- 239000011781 sodium selenite Substances 0.000 description 2
- 235000015921 sodium selenite Nutrition 0.000 description 2
- 229960001471 sodium selenite Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- 230000036575 thermal burns Effects 0.000 description 2
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical compound [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical group OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 235000019155 vitamin A Nutrition 0.000 description 2
- 239000011719 vitamin A Substances 0.000 description 2
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 2
- 235000005282 vitamin D3 Nutrition 0.000 description 2
- 239000011647 vitamin D3 Substances 0.000 description 2
- 229940045997 vitamin a Drugs 0.000 description 2
- 229940021056 vitamin d3 Drugs 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 235000013618 yogurt Nutrition 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 description 2
- 229960001763 zinc sulfate Drugs 0.000 description 2
- 229910001928 zirconium oxide Inorganic materials 0.000 description 2
- WTVHAMTYZJGJLJ-UHFFFAOYSA-N (+)-(4S,8R)-8-epi-beta-bisabolol Natural products CC(C)=CCCC(C)C1(O)CCC(C)=CC1 WTVHAMTYZJGJLJ-UHFFFAOYSA-N 0.000 description 1
- RGZSQWQPBWRIAQ-CABCVRRESA-N (-)-alpha-Bisabolol Chemical compound CC(C)=CCC[C@](C)(O)[C@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-CABCVRRESA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- LUKQUIZLFXGUKZ-UHFFFAOYSA-N (3-benzylidene-1,7,7-trimethyl-2-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonic acid Chemical compound CC1(C)C(C2=O)(C)CCC1(CS(O)(=O)=O)C2=CC1=CC=CC=C1 LUKQUIZLFXGUKZ-UHFFFAOYSA-N 0.000 description 1
- RLCKHJSFHOZMDR-UHFFFAOYSA-N (3R, 7R, 11R)-1-Phytanoid acid Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)CC(O)=O RLCKHJSFHOZMDR-UHFFFAOYSA-N 0.000 description 1
- AALXZHPCKJILAZ-UHFFFAOYSA-N (4-propan-2-ylphenyl)methyl 2-hydroxybenzoate Chemical compound C1=CC(C(C)C)=CC=C1COC(=O)C1=CC=CC=C1O AALXZHPCKJILAZ-UHFFFAOYSA-N 0.000 description 1
- DWANEFRJKWXRSG-UHFFFAOYSA-N 1,2-tetradecanediol Chemical compound CCCCCCCCCCCCC(O)CO DWANEFRJKWXRSG-UHFFFAOYSA-N 0.000 description 1
- QLAJNZSPVITUCQ-UHFFFAOYSA-N 1,3,2-dioxathietane 2,2-dioxide Chemical compound O=S1(=O)OCO1 QLAJNZSPVITUCQ-UHFFFAOYSA-N 0.000 description 1
- OVYMWJFNQQOJBU-UHFFFAOYSA-N 1-octanoyloxypropan-2-yl octanoate Chemical compound CCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC OVYMWJFNQQOJBU-UHFFFAOYSA-N 0.000 description 1
- LALVCWMSKLEQMK-UHFFFAOYSA-N 1-phenyl-3-(4-propan-2-ylphenyl)propane-1,3-dione Chemical compound C1=CC(C(C)C)=CC=C1C(=O)CC(=O)C1=CC=CC=C1 LALVCWMSKLEQMK-UHFFFAOYSA-N 0.000 description 1
- BEXQNGUXPFGRDC-UHFFFAOYSA-N 2,2-dimethoxy-1,3-diphenylpropane-1,3-dione Chemical compound C=1C=CC=CC=1C(=O)C(OC)(OC)C(=O)C1=CC=CC=C1 BEXQNGUXPFGRDC-UHFFFAOYSA-N 0.000 description 1
- WHQOKFZWSDOTQP-UHFFFAOYSA-N 2,3-dihydroxypropyl 4-aminobenzoate Chemical compound NC1=CC=C(C(=O)OCC(O)CO)C=C1 WHQOKFZWSDOTQP-UHFFFAOYSA-N 0.000 description 1
- YWRIATGSMAAKTP-UHFFFAOYSA-N 2,3-dihydroxypropyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)CO.CCCCCCCCCCCCCC(=O)OCC(O)CO YWRIATGSMAAKTP-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- GLHKHBCFIYOKAZ-UHFFFAOYSA-N 2-[(4-ethoxyanilino)methylidene]propanedioic acid Chemical compound CCOC1=CC=C(NC=C(C(O)=O)C(O)=O)C=C1 GLHKHBCFIYOKAZ-UHFFFAOYSA-N 0.000 description 1
- KXTAOXNYQGASTA-UHFFFAOYSA-N 2-benzylidenepropanedioic acid Chemical compound OC(=O)C(C(O)=O)=CC1=CC=CC=C1 KXTAOXNYQGASTA-UHFFFAOYSA-N 0.000 description 1
- TYYHDKOVFSVWON-UHFFFAOYSA-N 2-butyl-2-methoxy-1,3-diphenylpropane-1,3-dione Chemical compound C=1C=CC=CC=1C(=O)C(OC)(CCCC)C(=O)C1=CC=CC=C1 TYYHDKOVFSVWON-UHFFFAOYSA-N 0.000 description 1
- NCIAZCLIFWUDPR-UHFFFAOYSA-N 2-butyl-3,4,5,6-tetramethylphenol Chemical compound CCCCC1=C(C)C(C)=C(C)C(C)=C1O NCIAZCLIFWUDPR-UHFFFAOYSA-N 0.000 description 1
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- OSJVRHJQUTTZIN-UHFFFAOYSA-N 2-ethoxyethyl 2-methoxy-3-phenylprop-2-enoate Chemical compound CCOCCOC(=O)C(OC)=CC1=CC=CC=C1 OSJVRHJQUTTZIN-UHFFFAOYSA-N 0.000 description 1
- WSSJONWNBBTCMG-UHFFFAOYSA-N 2-hydroxybenzoic acid (3,3,5-trimethylcyclohexyl) ester Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C1=CC=CC=C1O WSSJONWNBBTCMG-UHFFFAOYSA-N 0.000 description 1
- WMJBVALTYVXGHW-UHFFFAOYSA-N 3,3-diphenylprop-2-enoic acid Chemical class C=1C=CC=CC=1C(=CC(=O)O)C1=CC=CC=C1 WMJBVALTYVXGHW-UHFFFAOYSA-N 0.000 description 1
- RLCKHJSFHOZMDR-PWCSWUJKSA-N 3,7R,11R,15-tetramethyl-hexadecanoic acid Chemical compound CC(C)CCC[C@@H](C)CCC[C@@H](C)CCCC(C)CC(O)=O RLCKHJSFHOZMDR-PWCSWUJKSA-N 0.000 description 1
- IPNFHEWNDOORKH-UHFFFAOYSA-N 6-methylheptyl 2-hydroxybenzoate Chemical compound CC(C)CCCCCOC(=O)C1=CC=CC=C1O IPNFHEWNDOORKH-UHFFFAOYSA-N 0.000 description 1
- HMFTYCPZFGBALI-UHFFFAOYSA-N 7-ethyloctadecan-7-yl 2,2-dimethylpropanoate Chemical compound CCCCCCCCCCCC(CC)(OC(=O)C(C)(C)C)CCCCCC HMFTYCPZFGBALI-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- HBMZNWKFVFUGND-UHFFFAOYSA-N CC1(C)C(C2=O)(C)CCC1(S(O)(=O)=O)C2=CC1=CC=CC=C1 Chemical compound CC1(C)C(C2=O)(C)CCC1(S(O)(=O)=O)C2=CC1=CC=CC=C1 HBMZNWKFVFUGND-UHFFFAOYSA-N 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 240000005109 Cryptomeria japonica Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 235000004866 D-panthenol Nutrition 0.000 description 1
- 239000011703 D-panthenol Substances 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108010082495 Dietary Plant Proteins Proteins 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 235000016623 Fragaria vesca Nutrition 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 238000006595 Griess deamination reaction Methods 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 206010023230 Joint stiffness Diseases 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- 240000005308 Juniperus chinensis Species 0.000 description 1
- 208000003456 Juvenile Arthritis Diseases 0.000 description 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108090000942 Lactalbumin Proteins 0.000 description 1
- 102000004407 Lactalbumin Human genes 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 1
- 241000473744 Medusantha martiusii Species 0.000 description 1
- 244000062730 Melissa officinalis Species 0.000 description 1
- 235000010654 Melissa officinalis Nutrition 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 240000009023 Myrrhis odorata Species 0.000 description 1
- 235000007265 Myrrhis odorata Nutrition 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- WYWZRNAHINYAEF-UHFFFAOYSA-N Padimate O Chemical compound CCCCC(CC)COC(=O)C1=CC=C(N(C)C)C=C1 WYWZRNAHINYAEF-UHFFFAOYSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 235000012550 Pimpinella anisum Nutrition 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- 241000283080 Proboscidea <mammal> Species 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 244000044822 Simmondsia californica Species 0.000 description 1
- 235000004433 Simmondsia californica Nutrition 0.000 description 1
- 239000004283 Sodium sorbate Substances 0.000 description 1
- 208000027520 Somatoform disease Diseases 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 235000019498 Walnut oil Nutrition 0.000 description 1
- NWGKJDSIEKMTRX-BFWOXRRGSA-N [(2r)-2-[(3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)C1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-BFWOXRRGSA-N 0.000 description 1
- QXNWVJOHUAQHLM-ROPPNANJSA-N [H]C12CCC3=C(C=C(O)C(C(C)C)=C3)[C@@]1(C)CCCC2(C)C Chemical compound [H]C12CCC3=C(C=C(O)C(C(C)C)=C3)[C@@]1(C)CCCC2(C)C QXNWVJOHUAQHLM-ROPPNANJSA-N 0.000 description 1
- ZRVDANDJSTYELM-UUSAFJCLSA-N [H]C12CCC3=C(C=CC(O)=C3C(C)C)[C@@]1(C)CCCC2(C)C Chemical compound [H]C12CCC3=C(C=CC(O)=C3C(C)C)[C@@]1(C)CCCC2(C)C ZRVDANDJSTYELM-UUSAFJCLSA-N 0.000 description 1
- TWZMQZBMHUHORI-FKIZINRSSA-N [H][C@@]12CCC3=C(C(=O)C(O)=C(C(C)C)C3=O)[C@@]1(C(=O)O)CCCC2(C)C Chemical compound [H][C@@]12CCC3=C(C(=O)C(O)=C(C(C)C)C3=O)[C@@]1(C(=O)O)CCCC2(C)C TWZMQZBMHUHORI-FKIZINRSSA-N 0.000 description 1
- VEJJMTHWRMKGKN-UIFIKXQLSA-N [H][C@@]12CCC3=C(C(C)C)C(O)=CC=C3[C@@]1(C)CCC[C@]2(C)C(=O)OC Chemical compound [H][C@@]12CCC3=C(C(C)C)C(O)=CC=C3[C@@]1(C)CCC[C@]2(C)C(=O)OC VEJJMTHWRMKGKN-UIFIKXQLSA-N 0.000 description 1
- ZJWKTCBVPIENRR-IIZPIQPGSA-N [H][C@@]12[C@@H]3OC(=O)C[C@@]1(CCCC2(C)C)C1=C(C=C(C(C)C)C(O)=C1O)[C@@H]3OC Chemical compound [H][C@@]12[C@@H]3OC(=O)C[C@@]1(CCCC2(C)C)C1=C(C=C(C(C)C)C(O)=C1O)[C@@H]3OC ZJWKTCBVPIENRR-IIZPIQPGSA-N 0.000 description 1
- VEUACKUBDLVUAC-UHFFFAOYSA-N [Na].[Ca] Chemical compound [Na].[Ca] VEUACKUBDLVUAC-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical class CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229930002945 all-trans-retinaldehyde Chemical class 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical class OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- RGZSQWQPBWRIAQ-LSDHHAIUSA-N alpha-Bisabolol Natural products CC(C)=CCC[C@@](C)(O)[C@@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-LSDHHAIUSA-N 0.000 description 1
- UBNYRXMKIIGMKK-RMKNXTFCSA-N amiloxate Chemical compound COC1=CC=C(\C=C\C(=O)OCCC(C)C)C=C1 UBNYRXMKIIGMKK-RMKNXTFCSA-N 0.000 description 1
- 229960002709 amiloxate Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000006053 animal diet Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 244000057196 artichoke thistle Species 0.000 description 1
- 235000016520 artichoke thistle Nutrition 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 229940071097 ascorbyl phosphate Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000001168 astaxanthin Substances 0.000 description 1
- 235000013793 astaxanthin Nutrition 0.000 description 1
- 229940022405 astaxanthin Drugs 0.000 description 1
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 229960005193 avobenzone Drugs 0.000 description 1
- 235000015173 baked goods and baking mixes Nutrition 0.000 description 1
- 229940002010 banana extract Drugs 0.000 description 1
- 239000002610 basifying agent Substances 0.000 description 1
- 239000010620 bay oil Substances 0.000 description 1
- 229960001716 benzalkonium Drugs 0.000 description 1
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 1
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical compound CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- 150000001565 benzotriazoles Chemical class 0.000 description 1
- WXNRYSGJLQFHBR-UHFFFAOYSA-N bis(2,4-dihydroxyphenyl)methanone Chemical compound OC1=CC(O)=CC=C1C(=O)C1=CC=C(O)C=C1O WXNRYSGJLQFHBR-UHFFFAOYSA-N 0.000 description 1
- DTVQVQGCVNNOSX-UHFFFAOYSA-N bis(2-ethylhexyl) 2-[(4-methoxyphenyl)methylidene]propanedioate Chemical compound CCCCC(CC)COC(=O)C(C(=O)OCC(CC)CCCC)=CC1=CC=C(OC)C=C1 DTVQVQGCVNNOSX-UHFFFAOYSA-N 0.000 description 1
- SODJJEXAWOSSON-UHFFFAOYSA-N bis(2-hydroxy-4-methoxyphenyl)methanone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=C(OC)C=C1O SODJJEXAWOSSON-UHFFFAOYSA-N 0.000 description 1
- YEAYGXLRPMKZBP-KQGICBIGSA-N bis(2-hydroxyethyl)azanium;(e)-3-(4-methoxyphenyl)prop-2-enoate Chemical compound OCCNCCO.COC1=CC=C(\C=C\C(O)=O)C=C1 YEAYGXLRPMKZBP-KQGICBIGSA-N 0.000 description 1
- 229940036350 bisabolol Drugs 0.000 description 1
- HHGZABIIYIWLGA-UHFFFAOYSA-N bisabolol Natural products CC1CCC(C(C)(O)CCC=C(C)C)CC1 HHGZABIIYIWLGA-UHFFFAOYSA-N 0.000 description 1
- FQUNFJULCYSSOP-UHFFFAOYSA-N bisoctrizole Chemical compound N1=C2C=CC=CC2=NN1C1=CC(C(C)(C)CC(C)(C)C)=CC(CC=2C(=C(C=C(C=2)C(C)(C)CC(C)(C)C)N2N=C3C=CC=CC3=N2)O)=C1O FQUNFJULCYSSOP-UHFFFAOYSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 239000001201 calcium disodium ethylene diamine tetra-acetate Substances 0.000 description 1
- 235000011188 calcium disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- SHWNNYZBHZIQQV-UHFFFAOYSA-L calcium;disodium;2-[2-[bis(carboxylatomethyl)azaniumyl]ethyl-(carboxylatomethyl)azaniumyl]acetate Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-L 0.000 description 1
- 229940075510 carbopol 981 Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 230000003846 cartilage breakdown Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000010627 cedar oil Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- 150000001783 ceramides Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000010630 cinnamon oil Substances 0.000 description 1
- 239000001926 citrus aurantium l. subsp. bergamia wright et arn. oil Substances 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000019545 cooked cereal Nutrition 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 235000019543 dairy drink Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- PWEOPMBMTXREGV-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2-diol Chemical compound CC(O)CO.CCCCCCCC(O)=O.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O.CCCCCCCCCC(O)=O PWEOPMBMTXREGV-UHFFFAOYSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960003949 dexpanthenol Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000007882 dietary composition Nutrition 0.000 description 1
- 235000020930 dietary requirements Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- WQQOKAKJKDTIBY-UHFFFAOYSA-N diethyl 2-[(4-ethoxyanilino)methylidene]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CNC1=CC=C(OCC)C=C1 WQQOKAKJKDTIBY-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- UVCJGUGAGLDPAA-UHFFFAOYSA-N ensulizole Chemical compound N1C2=CC(S(=O)(=O)O)=CC=C2N=C1C1=CC=CC=C1 UVCJGUGAGLDPAA-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- BMOAQMNPJSPXIU-UHFFFAOYSA-N ethyl 2-(3-fluoro-4-nitrophenyl)propanoate Chemical compound CCOC(=O)C(C)C1=CC=C([N+]([O-])=O)C(F)=C1 BMOAQMNPJSPXIU-UHFFFAOYSA-N 0.000 description 1
- IAJNXBNRYMEYAZ-UHFFFAOYSA-N ethyl 2-cyano-3,3-diphenylprop-2-enoate Chemical compound C=1C=CC=CC=1C(=C(C#N)C(=O)OCC)C1=CC=CC=C1 IAJNXBNRYMEYAZ-UHFFFAOYSA-N 0.000 description 1
- 229940068171 ethyl hexyl salicylate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 210000001145 finger joint Anatomy 0.000 description 1
- 125000004387 flavanoid group Chemical group 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000014106 fortified food Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940074050 glyceryl myristate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000015201 grapefruit juice Nutrition 0.000 description 1
- 235000013882 gravy Nutrition 0.000 description 1
- 239000007887 hard shell capsule Substances 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 229960004881 homosalate Drugs 0.000 description 1
- 150000002432 hydroperoxides Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000008407 joint function Effects 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- 235000021579 juice concentrates Nutrition 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 235000015122 lemonade Nutrition 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 239000004611 light stabiliser Substances 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000012661 lycopene Nutrition 0.000 description 1
- 229960004999 lycopene Drugs 0.000 description 1
- 239000001751 lycopene Substances 0.000 description 1
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- 239000011785 micronutrient Substances 0.000 description 1
- 235000013369 micronutrients Nutrition 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 235000020166 milkshake Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- GQEZCXVZFLOKMC-UHFFFAOYSA-N n-alpha-hexadecene Natural products CCCCCCCCCCCCCCC=C GQEZCXVZFLOKMC-UHFFFAOYSA-N 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 235000014571 nuts Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- YBGZDTIWKVFICR-UHFFFAOYSA-N octinoxate Chemical compound CCCCC(CC)COC(=O)C=CC1=CC=C(OC)C=C1 YBGZDTIWKVFICR-UHFFFAOYSA-N 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003349 osteoarthritic effect Effects 0.000 description 1
- 235000017802 other dietary supplement Nutrition 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 1
- 229960001173 oxybenzone Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000020737 peppermint extract Nutrition 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 230000004526 pharmaceutical effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- CGIHFIDULQUVJG-UHFFFAOYSA-N phytantriol Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)(O)C(O)CO CGIHFIDULQUVJG-UHFFFAOYSA-N 0.000 description 1
- CGIHFIDULQUVJG-VNTMZGSJSA-N phytantriol Natural products CC(C)CCC[C@H](C)CCC[C@H](C)CCC[C@@](C)(O)[C@H](O)CO CGIHFIDULQUVJG-VNTMZGSJSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229940013712 pineapple extract Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000004300 potassium benzoate Substances 0.000 description 1
- 235000010235 potassium benzoate Nutrition 0.000 description 1
- 229940103091 potassium benzoate Drugs 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- DCBSHORRWZKAKO-UHFFFAOYSA-N rac-1-monomyristoylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)CO DCBSHORRWZKAKO-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- NCYCYZXNIZJOKI-OVSJKPMPSA-N retinal group Chemical class C\C(=C/C=O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 1
- 229930002330 retinoic acid Chemical class 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 239000011607 retinol Chemical class 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical class CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 239000011770 retinyl acetate Chemical class 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 229940108325 retinyl palmitate Drugs 0.000 description 1
- 239000011769 retinyl palmitate Chemical class 0.000 description 1
- 235000019172 retinyl palmitate Nutrition 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 235000021309 simple sugar Nutrition 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 230000005808 skin problem Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- YRWWOAFMPXPHEJ-OFBPEYICSA-K sodium L-ascorbic acid 2-phosphate Chemical compound [Na+].[Na+].[Na+].OC[C@H](O)[C@H]1OC(=O)C(OP([O-])([O-])=O)=C1[O-] YRWWOAFMPXPHEJ-OFBPEYICSA-K 0.000 description 1
- 229940048058 sodium ascorbyl phosphate Drugs 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229940080237 sodium caseinate Drugs 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 1
- 235000019250 sodium sorbate Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000007886 soft shell capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000013322 soy milk Nutrition 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 229940071440 soy protein isolate Drugs 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000015149 toffees Nutrition 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical class [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- NMEPHPOFYLLFTK-UHFFFAOYSA-N trimethoxy(octyl)silane Chemical compound CCCCCCCC[Si](OC)(OC)OC NMEPHPOFYLLFTK-UHFFFAOYSA-N 0.000 description 1
- 229940094871 trimethoxycaprylylsilane Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004747 ubidecarenone Drugs 0.000 description 1
- 150000003669 ubiquinones Chemical class 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Chemical class O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 239000008170 walnut oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 235000008924 yoghurt drink Nutrition 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical class OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/18—Antioxidants, e.g. antiradicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/005—Preparations for sensitive skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention refers to the use of at least one tricyclic diterpenes for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
- Inflammatory disorders are one of the most important health problems in the world. Inflammation is in general a localized protective response of the body tissues to invasion of the host by foreign material or injurious stimuli.
- the causes of inflammation can be infectious agents such as bacteria, viruses, and parasites; or physical agents such as burns or radiation; or chemicals like toxins, drugs or industrial agents; or immunological reactions such as allergies and autoimmune responses or conditions associated with oxidative stress.
- Inflammation is characterized by pain, redness, swelling, heat, and eventual loss of function of the affected area. These symptoms are the results of a complex series of interactions taking place between the cells of the immune system. The response of the cells results in an interacting network of several groups of inflammatory mediators: Proteins (e.g. cytokines, enzymes (e.g. proteases, peroxydase), major basic protein, adhesion molecules (ICAM, VCAM), lipid mediators (e.g. eicosanoids, prostaglandins, leukotrienes, platelet activating factor (PAF)), reactive oxygen species (e.g. hydroperoxides, superoxyde anion O 2 ⁇ , nitric oxide (NO) etc).
- proteins e.g. cytokines, enzymes (e.g. proteases, peroxydase), major basic protein, adhesion molecules (ICAM, VCAM), lipid mediators (e.g. eicosanoids, prostaglandins, leukot
- Joint disorders are leading causes of disability and dysfunction in the elderly; almost 80% of people over age 60 show some evidence of these disorders. Age, genetic factors, muscle disuse and weakness, trauma, obesity and anatomical abnormalities contribute to the development of the disorder. Joint disorders can e.g. be caused by (chronic) inflammatory diseases of the joints as well as by cartilage degradation of one or several joints or a combination thereof. Cartilage degradation is defined within the framework of the invention as a metabolic disorder of joint cartilage characterized by increased production of cartilage-degrading enzymes such as matrix metalloproteases.
- Acute and chronic inflammation resulting from an excessive biosynthesis of inflammatory mediators is involved in numerous inflammatory disorders such as arthritis (e.g. osteoarthritis, rheumatoid arthritis), asthma, inflammatory bowel diseases, inflammatory diseases of the skin (e.g.
- contact dermatitis [particularly diaper area dermatitis], atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, acne, thermal and radiation burns such as sunburn, other types of skin inflammation, and the tissue-degenerating effects of aging) and chronic inflammatory disorders, such as atherosclerosis, heart diseases, metabolic syndrome X, osteoporosis, cancer, Alzheimer's disease and pre-stages thereof such as mild cognitive impairment or photoageing which is a result of chronic skin inflammation.
- Arthritis is a chronic (inflammatory) disease of the joints and encompasses many different forms.
- arthritis includes rheumatoid arthritis, spondyloarthopathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus and juvenile arthritis.
- rheumatoid arthritis is characterized at the molecular level by chronically unbalanced expression of cytokines, chemokines, kinins and their receptors, adhesion molecules and their respective receptors, as well as inflammatory enzymes.
- Osteoarthritis is a joint disease caused by the breakdown and loss of the cartilage of one or more joints which develops by wear and tear of the joints during aging and results in pain and diminished joint function. Symptoms of osteoarthritis include pain, stiffness and loss of mobility in one or more joints. Excessive joint loading increases the risk of osteoarthritis, hence osteoarthritis mostly affects the weight-bearing joints such as spine, knees and hips, but thumb and finger joints may also be affected. Joint disorders can also results from injury, i.e. microdamage or blunt trauma, fractures, damage to tendons, menisci or ligaments or can be the result of excessive mechanical stress or other biomechanical instability resulting from for example an injury or obesity.
- Psoriasis is one of the most common skin problems, affecting 1-3% of the human population.
- Inflammatory bowel disease is a general term used to describe gastrointestinal tract diseases and includes disorders such as ulcerative colitis and Crohn's disease.
- Atherosclerosis results from vascular injury which triggers inflammation.
- Activated macrophages, T-lymphocytes, and eventually smooth muscle cells are present in atherosclerotic plaques.
- Monocyte/macrophage and lymphocyte activation leads to the release of eicosanoids, cytokines and matrix metalloproteinases (MMPs) which are implicated in endothelial damage, as well as in the formation and eventually the rupture of atherosclerotic plaques.
- MMPs matrix metalloproteinases
- CRP C-reactive protein
- fibrinogen fibrinogen
- interleukins circulating inflammatory markers
- CRP C-reactive protein
- CAD coronary artery diseases
- Inflammatory processes are also associated with the pathophysiology of Alzheimer's disease. There is evidence of inflammation in the brain of patients with Alzheimer's disease, as it is characterized by increased levels of cytokines and activated microglial cells. Thus, inflammation is not only involved in the classical inflammatory disorders (e.g., arthritis, asthma, bowel diseases) but is also associated with many chronic inflammatory disorders (e.g., atherosclerosis, heart diseases, metabolic syndrome X, osteoporosis, cancer, Alzheimer disease).
- classical inflammatory disorders e.g., arthritis, asthma, bowel diseases
- chronic inflammatory disorders e.g., atherosclerosis, heart diseases, metabolic syndrome X, osteoporosis, cancer, Alzheimer disease.
- Inflammatory events are also associated with the pathophysiology of different types of cancers (e.g. gastric and intestinal cancers, melanomas). Increased levels of inflammatory mediators such as prostaglandins have been found in cancers of breast, colon, lung and pancreas in humans.
- cancers e.g. gastric and intestinal cancers, melanomas.
- Increased levels of inflammatory mediators such as prostaglandins have been found in cancers of breast, colon, lung and pancreas in humans.
- NSAIDs nonsteroidal anti-inflammatory drugs
- corticosteroids provide essentially symptomatic relief.
- Use of corticosteroids has declined due to a growing concern about the serious side effects of prolonged use.
- NSAIDs are among the most widely used drugs, primarily for the treatment of pain and inflammatory disorders, in particular for the treatment of arthritis (i.e. pain relief) but also for the treatment of cartilage degradation such as osteoarthritis.
- the drugs are given to control the pain and to restrain swelling, but do not prevent or treat damage to the cartilage.
- NSAIDs have a lower risk of developing Alzheimer's disease than those not taking NSAIDs.
- a protective effect of NSAIDs suggests that the cyclooxygenases might be involved in the neurodegenerative process.
- tricyclic diterpenes of formulae I and/or II have an anti-inflammatory activity and are suitable to treat or prevent cartilage loss and damage and can consequently be used as an agent suitable for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
- R 1 is hydrogen or C 1-6 -alkyl
- R 2 is hydroxy, C 3-5 -acyloxy, hydroxymethyl, 1,3-dihydroxypropyl or C 1-6 -alkyl
- R 3 and R 4 are independently from each other hydrogen, hydroxy, hydroxymethyl (—CH 2 —OH), C 1-5 -acyloxy or C 1-6 -alkoxy
- R 5 is C 1-6 -alkyl, hydroxymethyl, carboxy (CO 2 H) or methoxycarbonyl (CO 2 CH 3 )
- R 6 is hydrogen, or R 5 and R 6 together form a double bond
- R 7 and R 8 are independently from each other C 1-6 -alkyl, carboxy, x-hydroxy-C x -alkyl (with x being an integer from 1 to 6), or C 1-6 -alkoxycarbonyl (—CO 2 (C 1-6 -alkyl)) with the proviso that at least one of R 7 and R 8 is C 1-6 -alky
- the invention relates to the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 as given above for the manufacture of a nutraceutical or pharmaceutical in particular for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of inflammatory disorders such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, atherosclerosis, and osteoporosis, preferably of arthritis, in particular of osteoarthritis and rheumatoid arthritis.
- inflammatory disorders such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, atherosclerosis, and osteoporosis, preferably of arthritis, in particular of osteoarthritis and rheumatoid arthritis.
- the tricyclic diterpenes of the present invention are suitable for treatment, co-treatment and prevention of joint disorders in particular for reduction of joint inflammation, maintenance and/or improvement of joint health, prevention of joint stiffness, increase of joint mobility, providing supple and/or flexible joints, lubrication of the joints, relief of pain associated with joint inflammation, decrease of joint swelling, lessening joint problems, and providing joint care.
- the invention also relates to the use of at least one tricyclic diterpenes of formulae I and II with the definitions of R 1 to R 13 as given above for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of joint disorders.
- Preferred in all embodiments of the invention are tricyclic diterpenes of formulae I and/or II wherein
- tricyclic diterpene of formulae I and/or II also encompasses any material or extract of a plant containing at least one tricyclic diterpene of formulae I and II in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract.
- the terms “material of a plant” and “plant material” used in the context of the present invention mean any part of a plant.
- Carnosic acid 12-methyl ether means the racemic mixture as well as pure (4aR,10aS)-carnosic acid 12-methyl ether or pure (4aS,10aR)-carnosic acid 12-methyl ether or any mixture or diastereoisomer of them.
- Carnosic acid 12-methyl ether can be isolated from plants like sage, rosemary, Hyptis martiusii , but not limited to it. Therefore, any material or extract of these plants or any other plant material or extract containing carnosic acid 12-methyl ether in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e.
- Carnosic acid 12-methyl ether means both “natural” (isolated) and “synthetic” (manufactured) carnosic acid 12-methyl ether.
- 7-oxodehydroabietic acid means the racemic mixture as well as pure (1S,4aS,10aR)-7-oxodehydroabietic acid or pure (1R,4aR,10aS)-7-7-oxodehydroabietic acid or any mixture or diastereoisomer of them.
- 7-oxodehydroabietic acid can be isolated from plants like the following, but not limited to Cynara cardunculus ssp. cardunculus and Juniperus chinensis . Therefore, any material or extract of these plants or any other plant material or extract containing 7-oxodehydroabietic acid in an amount of at least 30 weight-% (i.e.
- 7-oxodehydroabietic acid means both “natural” (isolated) and “synthetic” (manufactured) 7-oxodehydroabietic acid.
- Totarol means the racemic mixture as well as pure (4bS,8aS)-totarol ((+)-totarol, trans-totarol) or pure (4bR,8aR)-totarol or any mixture or diastereoisomer of them.
- Totarol can be isolated from plants like the following, but not limited to sage, juniper and podocarpus sp. Therefore, any material or extract of these plants or any other plant material or extract containing totarol in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e.
- Totarol means both “natural” (isolated) and “synthetic” (manufactured) totarol. Totarol's synthesis is described in several articles, i.e. in Tetrahedron Letters 2003, 44(49), 8831-8835.
- 16-Hydroxytotarol means the racemic mixture as well as pure (1S,4aS,10aR)-16-hydroxytotarol or pure (1R,4aR,10aS)-16-hydroxytotarol or any mixture or diastereoisomer of them.
- 16-Hydroxytotarol can be isolated from the wood of Podocarpus species and other plants. Therefore, any material or extract of these plants or any other plant material or extract containing 16-hydroxytotarol in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e.
- 16-Hydroxytotarol means both “natural” (isolated) and “synthetic” (manufactured) 16-hydroxytotarol. 16-Hydroxytotarol's synthesis is described in several articles, i.e. in Journal of the Chemical Society, Abstracts 1963, 1553-1560 and in Chemistry & Industry (London, United Kingdom) 1963, 44, 1760-1761.
- Totarol-19-carboxylic acid methyl ester means the racemic mixture as well as pure (4aR,10aS)-totarol-19-carboxylic acid methyl ester or pure (4aR,10aS)-totarol-19-carboxylic acid methyl ester or any mixture or diastereoisomer of them.
- Totarol-19-carboxylic acid methyl ester can be isolated from the wood of Podocarpus species and other plants. Therefore, any material or extract of these plants or any other plant material or extract containing totarol-19-carboxylic acid methyl ester in an amount of at least 30 weight-% (i.e.
- Totarol-19-carboxylic acid methyl ester means both “natural” (isolated) and “synthetic” (manufactured) totarol-19-carboxylic acid methyl ester.
- Totarol-19-carboxylic acid methyl ester can be prepared according to the process described in Chemistry & Industry (London, United Kingdom) 1963, 44, 1760-1761.
- Sageone can be isolated from plants like the following, but not limited to sage, and other salivia sp. Therefore, any material or extract of these plants or any other plant material or extract containing sageone in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression.
- any material or extract of these plants or any other plant material or extract containing sageone in an amount of at least 30 weight-% i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-
- “Sageone” means both “natural” (isolated) and “synthetic” (manufactured) sageone. Sageone's synthesis is described e.g. in Journal of Organic Chemistry 1997, 62(20), 6928-6951.
- 8,11,13-Abietatriene-11,12,20-triol means the racemic mixture as well as pure (4bR,8aS)-8,11,13-abietatriene-11,12,20-triol or pure (4bS,8aR)-8,11,13-abietatriene-11,12,20-triol or any diastereoisomer or mixture of them.
- 8,11,13-Abietatriene-11,12,20-triol can be isolated from plants like Salivia sp. Without being limited thereto. Therefore, any material or extract of these plants or any other plant material or extract containing 8,11,13-abietatriene-11,12,20-triol in an amount of at least 30 weight-% (i.e.
- “Royleanonic acid” means the racemic mixture as well as pure (4aR,10aS)-royleanonic acid or pure (4aS,10aR)-royleanonic acid or any diastereoisomer or mixture of them.
- Royleanonic acid can be isolated from plants like sage ( Salvia sp.), but not limited to it. Therefore, any material or extract of these plants or any other plant material or extract containing royleanonic acid in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e.
- Royleanonic acid means both “natural” (isolated) and “synthetic” (manufactured) royleanonic acid.
- “Ferruginol” means pure (4bS,8aS)-ferruginol or pure (4bR,8aR)-ferruginol or any stereoisomer or mixture of them. Ferruginol can be isolated from plants like Cryptomeria sp., Juniperus sp., Salvia sp., but not limited to it. Therefore, any material or extract of these plants or any other plant material or extract containing ferruginol in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e.
- “Ferruginol” means both “natural” (isolated) and “synthetic” (manufactured) ferruginol. Ferruginol's synthesis is described in Organic Letters 2001, 3(11), 1737-1740.
- plant materials and plant extracts containing at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably at least 90 weight-% (i.e. from 90 to 100 weight-%), of these compounds, based on the total weight of the plant material/extract.
- treatment also encompasses co-treatment as well as prevention.
- prevention can be the prevention of the first occurrence (primary prevention) or the prevention of a reoccurence (secondary prevention).
- disorder also encompasses diseases.
- the dosage and ratios of the at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above to an animal including humans may vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired which can be determined by the expert in the field with normal trials, or with the usual considerations regarding the formulation of a nutraceutical.
- a suitable daily dosage of at least one tricyclic diterpene of formulae I and/or II, with the definitions of R 1 to R 13 and the preferences as given above for humans may be within the range of from 0.001 mg per kg body weight to about 40 mg per kg body weight per day. More preferred is a daily dosage of from about 0.01 to about 10 mg per kg body weight, and especially preferred is a daily dosage of from about 0.05 to 5.0 mg per kg body weight.
- the amount of a plant material or plant extract containing such tricyclic diterpene of formulae I and II with the definitions of R 1 to R 13 and the preferences as given above can be calculated accordingly.
- the tricyclic diterpene of formulae I and/or II is suitably present in an amount in the range of from about 0.1 mg to about 1000 mg, preferably in the range of from about 1 mg to about 500 mg per dosage unit.
- the invention also relates to tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences and definitions as given above for use as a medicament/composition for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or for the treatment, co-treatment or prevention of joint disorders.
- the invention relates to a nutraceutical comprising at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above and a nutraceutically acceptable carrier.
- a nutraceutical comprising at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above and a nutraceutically acceptable carrier for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders.
- the invention relates to a method for treatment, co-treatment and prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders in animals including humans said method comprising the step of administering an effective amount of at least one tricyclic diterpenes of formulae I and II with the definitions of R 1 to R 13 and the preferences as given above to animals including humans, which are in need thereof.
- the invention relates to a method for the regeneration and/or maintenance of (articular) cartilage in a mammal which comprises administering to a mammal in need of such regeneration and/or maintenance an effective amount of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 as given above.
- an effective amount refers to an amount necessary to obtain a physiological effect.
- the physiological effect may be achieved by one single dose or by repeated doses.
- the dosage administered may, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired and can be adjusted by a person skilled in the art.
- animals In the framework of the invention, with animals is meant all animals, including mammals, examples of which include humans. Preferred examples of mammals beside humans are non-ruminant or ruminant animals including cats, dogs, dromedaries, camels, elephants, and horses.
- nutraceutical as used herein include food product, foodstuff, dietary supplement, nutritional supplement or a supplement composition for a food product or a foodstuff.
- the present invention relates to a nutraceutical comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above in particular for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders
- the nutraceutical is a food product, foodstuff, dietary supplement, nutritional supplement or a supplement composition for a food product or a foodstuff preferably a dietary supplement, a nutritional supplement or a supplement composition for a food or a foodstuff.
- the term food product refers to any food or feed suitable for consumption by humans or animals.
- the food product may be a prepared and packaged food (e.g., mayonnaise, salad dressing, bread, or cheese food) or an animal feed (e.g., extruded and pelleted animal feed, coarse mixed feed or pet food composition).
- foodstuff refers to any substance fit for human or animal consumption.
- dietary supplement refers to a small amount of a compound for supplementation of a human or animal diet packaged in single or multiple dose units. Dietary supplements do not generally provide significant amounts of calories but may contain other micronutrients (e.g., vitamins or minerals).
- the term nutritional supplement refers to a composition comprising a dietary supplement in combination with a source of calories.
- nutritional supplements are meal replacements or supplements (e.g., nutrient or energy bars or nutrient beverages or concentrates).
- Food products or foodstuffs are for example beverages such as non-alcoholic and alcoholic drinks as well as liquid preparation to be added to drinking water and liquid food
- non-alcoholic drinks are for instance soft drinks, sport drinks, fruit juices, such as for example orange juice, apple juice and grapefruit juice; lemonades, teas, near-water drinks and milk and other dairy drinks such as for example yoghurt drinks, and diet drinks.
- food products or foodstuffs refer to solid or semi-solid foods comprising the composition according to the invention.
- These forms can include, but are not limited to baked goods such as cakes and cookies, puddings, dairy products, confections, snack foods, or frozen confections or novelties (e.g., ice cream, milk shakes), prepared frozen meals, candy, snack products (e.g., chips), liquid food such as soups, spreads, sauces, salad dressings, prepared meat products, cheese, yogurt and any other fat or oil containing foods, and food ingredients (e.g., wheat flour).
- baked goods such as cakes and cookies, puddings, dairy products, confections, snack foods, or frozen confections or novelties (e.g., ice cream, milk shakes), prepared frozen meals, candy, snack products (e.g., chips), liquid food such as soups, spreads, sauces, salad dressings, prepared meat products, cheese, yogurt and any other fat or oil containing foods, and food ingredients (e.g., wheat flour).
- food products or foodstuffs also includes functional foods and prepared food products, the latter referring to any pre-packaged food approved for human consumption.
- Animal feed including pet food compositions advantageously include food intended to supply necessary dietary requirements, as well as treats (e.g., dog biscuits) or other food supplements.
- the animal feed comprising the composition according to the invention may be in the form of a dry composition (for example, kibble), semi-moist composition, wet composition, or any mixture thereof.
- the animal feed is a supplement, such as a gravy, drinking water, yogurt, powder, suspension, chew, treat (e.g., biscuits) or any other delivery form.
- Dietary supplements of the present invention may be delivered in any suitable format.
- dietary supplements are formulated for oral delivery.
- the ingredients of the dietary supplement of this invention are contained in acceptable excipients and/or carriers for oral consumption.
- the actual form of the carrier, and thus, the dietary supplement itself, is not critical.
- the carrier may be a liquid, gel, gelcap, capsule, powder, solid tablet (coated or non-coated), tea, or the like.
- the dietary supplement is preferably in the form of a tablet or capsule and most preferably in the form of a hard (shell) gelatin capsule.
- Suitable excipient and/or carriers include maltodextrin, calcium carbonate, dicalcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid, croscarmellose sodium, sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose, methylcellulose, povidone, carboxymethylcellulose, corn starch, and the like (including mixtures thereof).
- Preferred carriers include calcium carbonate, magnesium stearate, maltodextrin, and mixtures thereof.
- the various ingredients and the excipient and/or carrier are mixed and formed into the desired form using conventional techniques.
- the tablet or capsule of the present invention may be coated with an enteric coating that dissolves at a pH of about 6.0 to 7.0.
- a suitable enteric coating that dissolves in the small intestine but not in the stomach is cellulose acetate phthalate. Further details on techniques for formulation for and administration may be found in the latest edition of Remington's Pharmaceutical Sciences (Maack Publishing Co., Easton, Pa.).
- the dietary supplement is provided as a powder or liquid suitable for adding by the consumer to a food or beverage.
- the dietary supplement can be administered to an individual in the form of a powder, for instance to be used by mixing into a beverage, or by stirring into a semi-solid food such as a pudding, topping, sauce, puree, cooked cereal, or salad dressing, for instance, or by otherwise adding to a food e.g. enclosed in caps of food or beverage container for release immediately before consumption.
- the dietary supplement may comprise one or more inert ingredients, especially if it is desirable to limit the number of calories added to the diet by the dietary supplement.
- the dietary supplement of the present invention may also contain optional ingredients including, for example, herbs, vitamins, minerals, enhancers, colorants, sweeteners, flavorants, inert ingredients, and the like.
- the dietary supplements further comprise vitamins and minerals including, but not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; vitamin D3; cyanocobalamin; sodium selenite; copper sulfate; vitamin A; vitamin C; inositol; potassium iodide.
- vitamins and minerals including, but not limited to, calcium phosphate or acetate, tribasic; potassium
- the present invention provides nutritional supplements (e.g., energy bars or meal replacement bars or beverages) comprising the composition according to the invention.
- the nutritional supplement may serve as meal or snack replacement and generally provides nutrient calories.
- the nutritional supplements provide carbohydrates, proteins, and fats in balanced amounts.
- the nutritional supplement can further comprise carbohydrate, simple, medium chain length, or polysaccharides, or a combination thereof.
- a simple sugar can be chosen for desirable organoleptic properties.
- Uncooked cornstarch is one example of a complex carbohydrate.
- the nutritional supplement contains, in one embodiment, combinations of sources of carbohydrate of three levels of chain length (simple, medium and complex; e.g., sucrose, maltodextrins, and uncooked cornstarch).
- Sources of protein to be incorporated into the nutritional supplement of the invention can be any suitable protein utilized in nutritional formulations and can include whey protein, whey protein concentrate, whey powder, egg, soy flour, soy milk, soy protein, soy protein isolate, caseinate (e.g., sodium caseinate, sodium calcium caseinate, calcium caseinate, potassium caseinate), animal and vegetable protein and hydrolysates or mixtures thereof.
- caseinate e.g., sodium caseinate, sodium calcium caseinate, calcium caseinate, potassium caseinate
- the biological value of the protein should be considered first, with the highest biological values being found in caseinate, whey, lactalbumin, egg albumin and whole egg proteins.
- the protein is a combination of whey protein concentrate and calcium caseinate.
- the nutritional supplement can also contain other ingredients, such as one or a combination of other vitamins, minerals, antioxidants, fiber and other dietary supplements (e.g., protein, amino acids, choline, lecithin, omega-3 fatty acids). Selection of one or several of these ingredients is a matter of formulation, design, consumer preference and end-user.
- the amounts of these ingredients added to the dietary supplements of this invention are readily known to the skilled artisan. Guidance to such amounts can be provided by the U.S. RDA doses for children and adults.
- vitamins and minerals that can be added include, but are not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; vitamin D3; cyanocobalamin; sodium selenite; copper sulfate; vitamin A; vitamin C; inositol; potassium iodide.
- the nutritional supplement can be provided in a variety of forms, and by a variety of production methods.
- the liquid ingredients are cooked; the dry ingredients are added with the liquid ingredients in a mixer and mixed until the dough phase is reached; the dough is put into an extruder, and extruded; the extruded dough is cut into appropriate lengths; and the product is cooled.
- the bars may contain other nutrients and fillers to enhance taste, in addition to the ingredients specifically listed herein.
- flavors, coloring agents, spices, nuts and the like may be incorporated into the nutraceutical composition.
- Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings, peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring.
- useful flavoring include, but are not limited to, pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, walnut oil, cherry oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch or toffee.
- the dietary supplement contains cocoa or chocolate.
- Emulsifiers may be added for stability of the nutraceutical.
- suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), and/or mono- and di-glycerides.
- Other emulsifiers are readily apparent to the skilled artisan and selection of suitable emulsifier(s) will depend, in part, upon the formulation and final product.
- Preservatives may also be added to the nutritional supplement to extend product shelf life.
- preservatives such as potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate or calcium disodium EDTA are used.
- the nutraceutical can contain natural or artificial (preferably low calorie) sweeteners, e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol.
- natural or artificial sweeteners e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol.
- artificial sweeteners can be desirable if the nutritional supplement is intended to be consumed by an overweight or obese individual, or an individual with type II diabetes who is prone to hyperglycemia.
- a multi-vitamin and mineral supplement may be added to the nutraceuticals of the present invention to obtain an adequate amount of an essential nutrient, which is missing in some diets.
- the multi-vitamin and mineral supplement may also be useful for disease prevention and protection against nutritional losses and deficiencies due to lifestyle patterns.
- the dosage and ratios of the at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above administered via a nutraceutical will, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired which can be determined by the expert in the field with normal trials, or with the usual considerations regarding the formulation of a nutraceutical.
- a nutraceutical according to the invention may comprise at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above in an amount of about 0.001 mg to 1 g, preferably in an amount from 0.01 mg to 1 g, most preferably in the range of 2.0 mg to 300 mg per serving.
- the at least one tricyclic diterpene of formulae I and/or II is suitably present in an amount in the range of from about 0.0001 (1 mg/kg) to about 5 weight-% (50 g/kg), preferably from about 0.001% (10 mg/kg) to about 1 weight-%, (10 g/kg) more preferably from about 0.01 (100 mg/kg) to about 0.5 weight-% (5 g/kg), based upon the total weight of the food or beverage.
- the amount of the tricyclic diterpene of formulae I and/or II, with the definitions of R 1 to R 13 and the preferences as given above is in the range of from 10 to 30 mg per serving, i.e. 120 mg per kg food or drink.
- a suitable daily dosage of a tricyclic diterpene of formulae I and/or II for the purposes of the present invention may be within the range of from 0.001 mg per kg body weight to about 1000 mg per kg body weight per day. More preferred is a daily dosage in the range of from about 0.1 mg to about 500 mg per kg body weight, and especially preferred is a daily dosage in the range of from about 1 mg to 100 mg per kg body weight.
- a plant material or plant extract comprising at least one tricyclic diterpene of formulae I and II with the definitions of R 1 to R 13 and the preferences as given above the dosages to be applied can be calculated accordingly.
- the invention relates to a pharmaceutical comprising the at least one tricyclic diterpene of formulae I and II with the definitions of R 1 to R 13 and preferences as given above and a pharmaceutically acceptable.
- a pharmaceutical comprising the at least one tricyclic diterpene of formulae I and II with the definitions of R 1 to R 13 and preferences as given above and a pharmaceutically acceptable the carrier for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders.
- Suitable pharmaceutical carriers are e.g. described in Remington's Pharmaceutical Sciences, supra, a standard reference text in this field.
- examples of such pharmaceutically acceptable carriers are both inorganic and organic carrier materials, suitable for oral/parenteral/injectable administration and include water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, and the like.
- the pharmaceutical may further comprise conventional pharmaceutical additives and adjuvants, excipients or diluents, including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
- conventional pharmaceutical additives and adjuvants, excipients or diluents including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
- the pharmaceutical is in the form of a powder, tablet, capsule, gel, liquid or solid embodiment.
- the dosages and ratios of the individual components in a pharmaceutical can be determined by the expert in the field with normal preclinical and clinical trials, or with the usual considerations regarding the formulation of pharmaceutical composition.
- the pharmaceutical may comprise the at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above in an amount from preferably 1 mg to 2000 mg per dosage unit, e.g., per capsule or tablet, or from 1 mg per daily dose to 3000 mg per daily dose of a liquid formulation.
- At least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above preferably in the form an enriched plant extract encompassing the at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above in an amount of at least 30 weight-% is administered via a pharmaceutical composition either in the form of a single dose or by multiple doses in an amount of at least 0.01 mg/kg bodyweight/day, preferably in an amount of 0.1-50 mg/kg body weight/day, most preferably in an amount of 0.3-15 mg/kg body weight/day.
- a plant material or plant extract comprising at least one tricyclic diterpene of formulae I and II with the definitions of R 1 to R 13 and the preferences as given above the dosages to be applied can be calculated accordingly.
- the nutraceuticals and pharmaceuticals according to the present invention may be in any galenic form that is suitable for administering to the animal body including the human body, more in particular in any form that is conventional for oral administration, e.g. in solid form, for example as (additives/supplements for) food or feed, food or feed premixes, fortified food or feed, tablets, pills, granules, dragées, capsules, and effervescent formulations such as powders and tablets, or in liquid form, for instance in the form of solutions, emulsions or suspensions, for example as beverages, pastes and oily suspensions.
- the pastes may be filled into hard or soft shell capsules. Examples for other application forms are forms for transdermal, parenteral, topical or injectable administration.
- nutraceutical and pharmaceutical compositions may be in the form of controlled (delayed) release formulations.
- Examples of pharmaceutical compositions also include compositions suitable for topical application and transdermal absorption of the phenolic compound, such as crèmes, gels, sprays, dry sticks, powders etc.
- a multi-vitamin and mineral supplement may be added to the nutraceuticals or pharmaceuticals of the present invention to obtain an adequate amount of an essential nutrient, which is missing in some diets.
- the multi-vitamin and mineral supplement may also be useful for disease prevention and protection against nutritional losses and deficiencies due to lifestyle patterns.
- Such pharmaceutically acceptable carriers are both inorganic and organic carrier materials, suitable for oral/parenteral/injectable administration and include water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, and the like.
- the pharmaceutical composition according to the present invention may further comprise conventional pharmaceutical additives and adjuvants, excipients or diluents, including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum Arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
- conventional pharmaceutical additives and adjuvants, excipients or diluents including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum Arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
- the at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above may be used in combination with other nutraceutical compositions or therapeutic agents known to those skilled in the art for treatment or prevention of inflammatory disorder and 7 or joint disorders by administration prior to, simultaneously with or following the administration of the at least one tricyclic diterpene of formulae I and/or II with the definitions of R 1 to R 13 and preferences as given above.
- the present invention not only the tricyclic diterpenes of the formulae I and II themselves, with the definitions of R 1 to R 13 and the preferences as given above, but also plant materials and extracts containing them in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e.
- the invention also relates to the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory disorders of the skin such as sunburn, impure skin such as acne or the results of chronic skin inflammation such as photoageing.
- composition comprising the at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory disorders of the skin such as sunburn, impure skin such as acne or the results of chronic skin inflammation such as photoageing may be designed for oral delivery such as a nutraceutical or a medicament or may be for topical application such as a cream or lotion without being limited hereto.
- the invention relates to a cosmetic or dermatological preparation (the latter preparation are a specific type of a pharmaceutical) comprising an effective amount of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above or compositions containing them (plant materials/extracts containing them in an amount of at least 30 weight-%, preferably in an amount of at least 50 weight-%, more preferably in an amount of from 70 to 90 weight-%, most preferably in an amount of at least 90 weight-%, based on the total weight of the plant material or extract; dietary/pharmaceutical compositions) and a cosmetically or dermatologically acceptable carrier.
- the cosmetic or dermatological composition may further comprise conventional cosmetic respectively dermatological adjuvants and/or additives and/or additional active ingredients.
- the cosmetic or dermatological preparations are skin care formulations for the treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn caused by UV-radiation, of contact dermatitis (particularly diaper area dermatitis), atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, thermal burns, photoageing or for the treatment, co-treatment or prevention of impure skin such as acne.
- impure skin include pimples, acne and other skin impurities with an inflammatory aspect.
- the invention also relates to a composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory skin conditions.
- the composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory skin conditions may be designed for oral administration such as e.g. a nutraceutical or a pharmaceutical or a medicament or may be designed for topical application such as a cream or lotion without being limited hereto.
- composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory conditions of the skin is intended for oral administration it may be in the form of a nutraceutical or a pharmaceutical with all the definitions and preferences as given above. Such products are also known as beauty foods and supplements. If the composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory conditions of the skin is intended for topical application it may be in the form of a cosmetic or dermatological preparation as described herein.
- inflammatory skin conditions encompasses inflammatory diseases of the skin such as e.g. contact dermatitis [particularly diaper area dermatitis], atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, acne, thermal and radiation burns such as sunburn as well as any other types of skin inflammation such as e.g. photoageing which is a result of chronic skin inflammation.
- the term ‘inflammatory skin conditions’ also encompasses the term ‘Impure skin’. “Impure skin’ can be caused by various factors: skin irritation through various exogenous and endogenous stimuli (e.g.
- cytokines play an important role.
- Pro-inflammatory cytokines are released from keratinocytes in the epidermis upon inflammatory stimuli (Boniface K, Lecron J C, Bernard F X, Dagregorio G, Guillet G, Nau F, Morel F. Keratinocytes as targets for interleukin-10-related cytokines: a putative role in the pathogenesis of psoriasis, Eur. Cytokine Netw. 2005 December; 16(4):309-19).
- the invention also relates to the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for promoting an optimal health, natural radiance and glow and/or a beautiful look of the skin. Furthermore, the invention encompasses the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R 1 to R 13 and the preferences as given above for supporting a clear, pure appearance of the skin.
- the term “effective amount” means preferably at least 0.001% of each active agents based on the total weight of the cosmetic or dermatological composition.
- the cosmetic or dermatological preparations comprise the active agents selected from the list above in an amount between 0.01 wt.-% and 20 wt.-%, more preferably between 0.05 and 10 wt.-%, still more preferably between 0.1 and 5 wt.-%.
- the amount of the cosmetic or dermatological preparation which is to be applied to the skin depends on the concentration of the active ingredients in the preparation and the desired cosmetic or pharmaceutical effect.
- the application can be such that a crème is applied to the skin.
- a crème is usually applied in an amount of about 1 to 2 mg crème/cm 2 skin.
- the amount of the composition which is applied to the skin is, however, not critical, and if with a certain amount of applied composition the desired effect cannot be achieved, a higher concentration of the active preparations which contain more active ingredient might be employed.
- the invention also relates to the use of the cosmetic preparation for the cosmetic treatment, co-treatment or prevention of inflammation of the skin, in particular for the cosmetic treatment, co-treatment or prevention of sunburn, contact dermatitis (particularly diaper area dermatitis), atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, thermal burns or photoageing as well as of sensitive skin towards environmental stressors (such as wind, soaps, dry climate).
- the invention relates to a method for the treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn in humans, of impure skin such as for example acne or of photoageing which is associated with chronic skin inflammation, said method comprising the step of administering an effective amount of the dermatological composition according to the invention to humans, which are in need thereof.
- the invention relates to a method for cosmetic treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn or of impure skin such as acne by a cosmetic preparation according to the invention. Sunburn prevention is preferably achieved with topical application comprising the composition of the invention preferably in combination with suitable light screening agents.
- the cosmetic or dermatological preparations according to the invention may be in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of O/W or W/O type, O/W/O or W/O/W-type, wherein O stands for oil phase and wherein W stands for water phase), such as a cream, a paste, a lotion, a thickened lotion or a milk, a vesicular dispersion in the form of an ointment, a gel, a solid tube stick or an aerosol mousse, and may be provided in the form of a mousse, foam or a spray foams, sprays, sticks or aerosols or wipes.
- an emulsion or micro emulsion in particular of O/W or W/O type, O/W/O or W/O/W-type, wherein O stands for oil phase and wherein W stands for water phase
- cosmetic or dermatological preparations are skin care preparations, in particular, body oils, body lotions, body gels, treatment creams, skin protection ointments, moisturizing gels, moisturizing sprays, revitalizing body sprays, after sun preparations or sunscreen formulations.
- the cosmetic or dermatological composition for the treatment, co-treatment or prevention of inflammation of the skin may be in a form that is conventional for oral administration, examples of which are described above and also include beauty foods and supplements.
- the cosmetic or dermatological preparations of the invention for instance as sunscreen formulations or after sun preparations may further comprise the usual cosmetic respectively dermatological adjuvants and/or additives such as preservatives/antioxidants, fatty substances/oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, additional light screening agents, antifoaming agents, moisturizers, fragrances, surfactants, fillers, sequestering agents, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorants, pigments or nanopigments, light stabilizers, insect repellants, skin tanning agents, skin whitening agents, antibacterial agents, preservatives active ingredients or any other ingredients usually formulated into cosmetics.
- preservatives/antioxidants fatty substances/oils
- water organic solvents
- silicones thickeners
- softeners emulsifiers
- additional light screening agents antifoaming agents
- Light screening agents which may be incorporated into cosmetic or dermatological preparations of the invention for instance sunscreen formulations are advantageously selected from IR, UV-A, UV-B, UV-C and/or broadband filters.
- UV-B or broad spectrum screening agents i.e. substances having absorption maxima between about 290 and 340 nm may be organic or inorganic compounds.
- Organic UV-B or broadband screening agents are e.g.
- acrylates such as 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (octocrylene, PARSOL® 340), ethyl 2-cyano-3,3-diphenylacrylate and the like; camphor derivatives such as 4-methyl benzylidene camphor (PARSOL® 5000), 3-benzylidene camphor, camphor benzalkonium methosulfate, polyacrylamidomethyl benzylidene camphor, sulfo benzylidene camphor, sulphomethyl benzylidene camphor, therephthalidene dicamphor sulfonic acid and the like; Cinnamate derivatives such as ethylhexyl methoxycinnamate (PARSOL® MCX), ethoxyethyl methoxycinnamate, diethanolamine methoxycinnamate (PARSOL® Hydro), isoamyl methoxycinnamate and the like as
- 2-phenyl benzimidazole sulfonic acid and its salts PARSOL®HS.
- Salts of 2-phenyl benzimidazole sulfonic acid are e.g. alkali salts such as sodium- or potassium salts, ammonium salts, morpholine salts, salts of primary, sec. and tert.
- salicylate derivatives such as isopropylbenzyl salicylate, benzyl salicylate, butyl salicylate, ethylhexyl salicylate (PARSOL® EHS, NEO Heliopan OS), isooctyl salicylate or homomethyl salicylate (homosalate, PARSOL® HMS, NEO Heliopan OS) and the like; triazine derivatives such as ethylhexyl triazone (Uvinul T-150), diethylhexyl butamido triazone (Uvasorb HEB).
- salicylate derivatives such as isopropylbenzyl salicylate, benzyl salicylate, butyl salicylate, ethylhexyl salicylate (PARSOL® EHS, NEO Heliopan OS), isooctyl salicylate or homomethyl salicylate (homosalate, PARSOL® HMS, NEO Heliopan OS) and the
- Encapsulated UV-filters such as encapsulated ethylhexyl methoxycinnamate (Eusolex UV-pearls) or microcapsules loaded with UV-filters as e.g. disclosed in EP 1471995 and the like.
- Inorganic compounds are pigments such as microparticulated TiO 2 , ZnO and the like.
- the term “microparticulated” refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm.
- the TiO 2 particles may also be coated by metal oxides such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art.
- Examples of broad spectrum or UV A screening agents i.e. substances having absorption maxima between about 320 and 400 nm may be organic or inorganic compounds e.g. dibenzoylmethane derivatives such as 4-tert. butyl-4′-methoxydibenzoyl-methane (PARSOL® 1789), dimethoxydibenzoylmethane, isopropyldibenzoylmethane and the like; benzotriazole derivatives such as 2,2′-methylene-bis-(6-(2H-benzotriazole-2-yl)-4-(1,1,3,3,-tetramethylbutyl)-phenol (TINOSORB M) and the like; bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S) and the like; phenylene-1,4-bis-benzimidazolsulfonic acids or salts such as 2,2-(1,4-phenylene)bis-(1H
- microparticulated refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm.
- the particles may also be coated by other metal oxides such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art.
- the term “conventional UV-A screening agent” also refers to dibenzoylmethane derivatives such as e.g. PARSOL® 1789 stabilized by, e.g. 3,3-Diphenylacrylate derivatives as described in the European Patent Publications EP 0 514 491 B1 and EP 0 780 119 A1; Benzylidene camphor derivatives as described in the U.S. Pat. No. 5,605,680; Organosiloxanes containing benzmalonate groups as described in the European Patent Publications EP 0358584 B1, EP 0538431 B1 and EP 0709080 A1.
- PARSOL® 1789 stabilized by, e.g. 3,3-Diphenylacrylate derivatives as described in the European Patent Publications EP 0 514 491 B1 and EP 0 780 119 A1
- Benzylidene camphor derivatives as described in the U.S. Pat. No. 5,605,680
- Active ingredients which may be included in the cosmetic or dermatological preparations of the invention are for example vitamins and derivatives thereof, for example tocopherol, tocopherol acetate, ascorbic acid, ascorbyl phosphate, vitamin Q, D, and K, retinol, retinal, retinoic acid, retinol acetate, retinol palmitate, biotin, carotenoid derivatives such as beta-carotene, lycopene, astaxanthin, vegetable extracts, antibacterial ingredients, instable amino acids comprising dipeptides, oligopeptides and polypeptides such as methionine, cysteine, cystine, tryptophan, phenylalanine, tyrosine, phenols, polyphenols or flavanoids, bisabolol, allantoin, phytantriol, panthenol, AHA acids, ubiquinones such as coenzyme Q 10, ceramides, pseudoceramides, essential oils, plant extracts de
- the necessary amounts of the cosmetic and dermatological adjuvants, additives and/or additional active ingredients can, based on the desired product, easily be chosen by a person skilled in the art and will be illustrated in the examples, without being limited hereto.
- the Sageone (VII) and 8,11,13-Abietatriene-11,12,20-triol (in the following referred to Abietatrienetriol) (VIII) were obtained from Analyticon, carnosic acid 12-methylether (XI) was isolated from a lipophilic extract of rosemary needles by chromatography in a purity >95%.
- nitric oxide and/or proinflammatory prostaglandins PGE 2 plays a critical role in the inflammation process, while nitric oxide (NO) is a hallmark of inflammation in various chronic inflammatory diseases including various forms of arthritis, gastro-intestinal diseases and metabolic syndrome.
- the compounds were dissolved in DMSO in concentrated form and did not contain byproducts that interfered with the assays.
- Final vehicle (DMSO) concentration did not exceed 0.2% v/v in the assays.
- the anti-inflammatory effects of compounds was tested in cellular assays using a murine macrophage indicator cell line, RAW267.7, which was purchased from American Type Culture Collection, (ATCC) and cultured in DMEM according to the protocol provided by ATCC.
- Cells ( ⁇ 50'000/well) were seeded into flat-bottomed microtiter plates and cultured for one day. Cells were then starved in complete medium containing 0.25% fetal calf serum (FCS) (D-025). After overnight culture, medium was removed and replaced by 100 ⁇ L of D-025 containing the test compounds at twice the final concentration.
- FCS fetal calf serum
- LPS lipopolysaccharide
- ECM extracellular matrix
- MMPs matrix metalloproteinases
- the cells were treated with IL-1 ⁇ , which is one of the natural mediators that induce cartilage breakdown and is detected in substantial amounts in osteoarthritic cartilage tissues and cells derived thereof.
- Treatment of cells with IL-1 ⁇ triggers the expression of genes that are involved in catabolic events, such as MMPs. Also, treatment of the cells with IL-1 ⁇ reduces the collagen expression levels (compared to untreated cells)
- Chondrocytes (SW1353; purchased from the American Tissue Culture Collection [ATCC]) were grown in cell culture medium according to the instructions from ATCC. For experimental treatments, cells were seeded into 6-well plates and cultured for two days until they reached confluence. Total cellular RNA was extracted from cultured cells and reverse-transcribed as described by Richard et al. Mol. Nutr. Food Res. 49, 431-442, 2005. Expression levels of distinct genes were determined by quantitative real-time PCR as described in Richard et al. Mol. Nutr. Food Res. 49, 431-442, 2005. Results of this experiment are shown in Table 2 below:
- Soft gelatin capsules are prepared by conventional procedures providing a dose of Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) of 10 mg.
- a suitable daily dose is 1 to 5 capsules.
- glycerol Water, gelatine, vegetable oil
- Hard gelatin capsules are prepared by conventional procedures providing a dose of Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) of 20 mg.
- a suitable daily dose is 1 to 5 capsules.
- Fillers lactose or cellulose or cellulose derivatives q.s.
- Lubricant magnesium stearate if necessary (0.5%)
- Tablets are prepared by conventional procedures providing as active ingredient 20 mg of Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) per tablet, and as excipients microcrystalline cellulose, silicone dioxide (SiO 2 ), magnesium stearate, crospovidone NF (which is a disintegration agent) ad 500 mg.
- Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) per tablet, and as excipients microcrystalline cellulose, silicone dioxide (SiO 2 ), magnesium stearate, crospovidone NF (which is a disintegration agent) ad 500 mg.
- a soft drink containing a Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) may be prepared as follows:
- a soft drink is prepared from the following ingredients:
- Fruit juice concentrates and water soluble flavours are mixed without incorporation of air.
- the color is dissolved in deionized water.
- Ascorbic acid and citric acid are dissolved in water.
- Sodium benzoate is dissolved in water.
- the pectin is added under stirring and dissolved while boiling. The solution is cooled down.
- Orange oil and oil soluble flavours are premixed.
- the active ingredient as mentioned under F is stirred into the fruit juice concentrate mixture of A.
- ROVIMIX® STAY-C® 35 from DSM Nutritional Products AG
- Vitamin E and beta-carotene and carnosic acid-12-methylether are incorporated in an amount sufficient to provide 30 mg ROVIMIX® STAY-C® 35/kg, and 300 IU vitamin E/kg and 280 mg beta-carotene/kg and 100 mg of carnosic acid-12-methylether in the final food composition before extruding the entire blend.
- the food composition is dried to contain dry matter of about 90% by weight.
- ROPUFA as supplied by DSM Nutritional Products
- ROVIMIX® STAY-C® 35 from DSM Nutritional Products AG
- Vitamin E and beta-carotene and sageone are incorporated in an amount sufficient to provide 30 mg ROVIMIX® STAY-C® 35 kg, and 300 IU vitamin E/kg and 280 mg beta-carotene/kg and 200 mg/kg of sageone in the final food composition before cooking the entire blend.
- the food composition is dried to contain a dry matter of about 90% by weight.
- a Dermatological Composition Comprising a Tricyclic Diterpene of Formulae I and/or II Such as Carnosic Acid 12-Methylether (XI) (Treatment Cream) which May be Used for (Cosmetic) Treatment of Inflammation of the Skin Caused by Sunburn
- XI Carnosic Acid 12-Methylether
- a treatment cream may be prepared with the following ingredients, in the following amounts:
- Triethanolamine 2.50 D) Tricyclic diterpene of For example carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI)
Abstract
The present invention refers to the use of at least one tricyclic diterpenes for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
Description
- The present invention refers to the use of at least one tricyclic diterpenes for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
- Inflammatory disorders are one of the most important health problems in the world. Inflammation is in general a localized protective response of the body tissues to invasion of the host by foreign material or injurious stimuli. The causes of inflammation can be infectious agents such as bacteria, viruses, and parasites; or physical agents such as burns or radiation; or chemicals like toxins, drugs or industrial agents; or immunological reactions such as allergies and autoimmune responses or conditions associated with oxidative stress.
- Inflammation is characterized by pain, redness, swelling, heat, and eventual loss of function of the affected area. These symptoms are the results of a complex series of interactions taking place between the cells of the immune system. The response of the cells results in an interacting network of several groups of inflammatory mediators: Proteins (e.g. cytokines, enzymes (e.g. proteases, peroxydase), major basic protein, adhesion molecules (ICAM, VCAM), lipid mediators (e.g. eicosanoids, prostaglandins, leukotrienes, platelet activating factor (PAF)), reactive oxygen species (e.g. hydroperoxides, superoxyde anion O2 −, nitric oxide (NO) etc). However, many of those mediators of inflammation are also regulators of normal cellular activity. Thus, deficiencies of inflammatory reactions lead to a compromised host (i.e. infection) while uncontrolled and thus chronic inflammation leads to inflammatory diseases mediated in part by the excessive production of several of the above mentioned mediators.
- Joint disorders are leading causes of disability and dysfunction in the elderly; almost 80% of people over age 60 show some evidence of these disorders. Age, genetic factors, muscle disuse and weakness, trauma, obesity and anatomical abnormalities contribute to the development of the disorder. Joint disorders can e.g. be caused by (chronic) inflammatory diseases of the joints as well as by cartilage degradation of one or several joints or a combination thereof. Cartilage degradation is defined within the framework of the invention as a metabolic disorder of joint cartilage characterized by increased production of cartilage-degrading enzymes such as matrix metalloproteases.
- Acute and chronic inflammation resulting from an excessive biosynthesis of inflammatory mediators is involved in numerous inflammatory disorders such as arthritis (e.g. osteoarthritis, rheumatoid arthritis), asthma, inflammatory bowel diseases, inflammatory diseases of the skin (e.g. contact dermatitis [particularly diaper area dermatitis], atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, acne, thermal and radiation burns such as sunburn, other types of skin inflammation, and the tissue-degenerating effects of aging) and chronic inflammatory disorders, such as atherosclerosis, heart diseases, metabolic syndrome X, osteoporosis, cancer, Alzheimer's disease and pre-stages thereof such as mild cognitive impairment or photoageing which is a result of chronic skin inflammation.
- Arthritis is a chronic (inflammatory) disease of the joints and encompasses many different forms. For example, arthritis includes rheumatoid arthritis, spondyloarthopathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus and juvenile arthritis. Like asthma, rheumatoid arthritis is characterized at the molecular level by chronically unbalanced expression of cytokines, chemokines, kinins and their receptors, adhesion molecules and their respective receptors, as well as inflammatory enzymes.
- Osteoarthritis is a joint disease caused by the breakdown and loss of the cartilage of one or more joints which develops by wear and tear of the joints during aging and results in pain and diminished joint function. Symptoms of osteoarthritis include pain, stiffness and loss of mobility in one or more joints. Excessive joint loading increases the risk of osteoarthritis, hence osteoarthritis mostly affects the weight-bearing joints such as spine, knees and hips, but thumb and finger joints may also be affected. Joint disorders can also results from injury, i.e. microdamage or blunt trauma, fractures, damage to tendons, menisci or ligaments or can be the result of excessive mechanical stress or other biomechanical instability resulting from for example an injury or obesity.
- Psoriasis is one of the most common skin problems, affecting 1-3% of the human population. Inflammatory bowel disease is a general term used to describe gastrointestinal tract diseases and includes disorders such as ulcerative colitis and Crohn's disease.
- Beside the process of intravascular lipid deposition, inflammatory reactions of the endothelial (i.e. blood vessel) wall are considered to critically contribute to atherosclerosis i.e. atheroma formation. Atherosclerosis results from vascular injury which triggers inflammation. Activated macrophages, T-lymphocytes, and eventually smooth muscle cells are present in atherosclerotic plaques. Monocyte/macrophage and lymphocyte activation leads to the release of eicosanoids, cytokines and matrix metalloproteinases (MMPs) which are implicated in endothelial damage, as well as in the formation and eventually the rupture of atherosclerotic plaques. Finally, circulating inflammatory markers such as C-reactive protein (CRP), fibrinogen, and interleukins are increased or altered in groups at high-risk of coronary artery diseases (CAD). Several clinical trials indicate that elevated CRP concentration correlates with increased risk of coronary, and vascular, events. Thus inflammation appears to play an important role in the initiation and progression of atheroma formation.
- Inflammatory processes are also associated with the pathophysiology of Alzheimer's disease. There is evidence of inflammation in the brain of patients with Alzheimer's disease, as it is characterized by increased levels of cytokines and activated microglial cells. Thus, inflammation is not only involved in the classical inflammatory disorders (e.g., arthritis, asthma, bowel diseases) but is also associated with many chronic inflammatory disorders (e.g., atherosclerosis, heart diseases, metabolic syndrome X, osteoporosis, cancer, Alzheimer disease).
- Inflammatory events are also associated with the pathophysiology of different types of cancers (e.g. gastric and intestinal cancers, melanomas). Increased levels of inflammatory mediators such as prostaglandins have been found in cancers of breast, colon, lung and pancreas in humans.
- Currently, two main classes of drugs, the corticosteroid and the nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammatory disorders and/or joint disorders. NSAIDs and corticosteroids provide essentially symptomatic relief. Use of corticosteroids has declined due to a growing concern about the serious side effects of prolonged use.
- NSAIDs are among the most widely used drugs, primarily for the treatment of pain and inflammatory disorders, in particular for the treatment of arthritis (i.e. pain relief) but also for the treatment of cartilage degradation such as osteoarthritis. However, in the latter case, the drugs are given to control the pain and to restrain swelling, but do not prevent or treat damage to the cartilage.
- Epidemiological studies have suggested that patients taking NSAIDs have a lower risk of developing Alzheimer's disease than those not taking NSAIDs. A protective effect of NSAIDs suggests that the cyclooxygenases might be involved in the neurodegenerative process.
- Epidemiological studies showed a significant reduction in the risk of colorectal, gastric, esophageal, and breast cancers among people who take NSAIDs compared with those not taking NSAIDs. In animal models, NSAIDs significantly reduced tumor development.
- However, long-term use of NSAIDs when treating chronic diseases such as arthritis or osteoarthritis is limited by severe side-effects like serious gastrointestinal complications, renal toxicity or asthmatic reactions.
- For these reasons patients with inflammatory diseases and/or joint disorders have a special interest in a type of treatment considered as “natural” with mild anti-inflammatory effects and without major side effects, which can be used for disease prevention and as adjuvant treatment. Even though there are examples of “natural” agents with shown anti-inflammatory action these “natural” compounds often have an inadequate biological and thus inhibitory activity.
- For the reasons outlined above, there is a great need for new anti-inflammatory agents and agents that treat joint disorders e.g. caused by cartilage degradation.
- Surprisingly it has been found that tricyclic diterpenes of formulae I and/or II have an anti-inflammatory activity and are suitable to treat or prevent cartilage loss and damage and can consequently be used as an agent suitable for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
- wherein R1 is hydrogen or C1-6-alkyl;
R2 is hydroxy, C3-5-acyloxy, hydroxymethyl, 1,3-dihydroxypropyl or C1-6-alkyl;
R3 and R4 are independently from each other hydrogen, hydroxy, hydroxymethyl (—CH2—OH), C1-5-acyloxy or C1-6-alkoxy;
R5 is C1-6-alkyl, hydroxymethyl, carboxy (CO2H) or methoxycarbonyl (CO2CH3);
R6 is hydrogen, or R5 and R6 together form a double bond;
R7 and R8 are independently from each other C1-6-alkyl, carboxy, x-hydroxy-Cx-alkyl (with x being an integer from 1 to 6), or C1-6-alkoxycarbonyl (—CO2(C1-6-alkyl)) with the proviso that at least one of R7 and R8 is C1-6-alkyl;
R9 is hydrogen, hydroxymethyl, methoxy, oxo or C1-5-acyloxy;
R10 is hydrogen or R5 and R10 taken together are —CO—O—, —O—CO—, —CH2—O— or —O—CH2—;
R11 and R12 are both hydrogen or R11 and R12 together are oxo;
R13 is C1-6-alkyl, hydroxymethyl, carboxy (CO2H) or methoxycarbonyl (CO2CH3) or R6 and R13 taken together form a double bond
with the further proviso for formula I that if R2 is hydroxy R1 is C1-6-alkyl. - Thus, the invention relates to the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 as given above for the manufacture of a nutraceutical or pharmaceutical in particular for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of inflammatory disorders such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, atherosclerosis, and osteoporosis, preferably of arthritis, in particular of osteoarthritis and rheumatoid arthritis.
- Also, the tricyclic diterpenes of the present invention are suitable for treatment, co-treatment and prevention of joint disorders in particular for reduction of joint inflammation, maintenance and/or improvement of joint health, prevention of joint stiffness, increase of joint mobility, providing supple and/or flexible joints, lubrication of the joints, relief of pain associated with joint inflammation, decrease of joint swelling, lessening joint problems, and providing joint care. Thus, the invention also relates to the use of at least one tricyclic diterpenes of formulae I and II with the definitions of R1 to R13 as given above for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of joint disorders.
- Further objects of the present invention are the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 as given above as cartilage-regenerating and -maintaining agent as well as the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 as given above (for the manufacture of a composition) for the maintenance and regeneration of articular cartilage.
- Preferred in all embodiments of the invention are tricyclic diterpenes of formulae I and/or II wherein
-
- R1 is hydrogen or iso-propyl;
- R2 is hydroxy or iso-propyl;
- R3 and R4 are independently from each other hydrogen, hydroxy or methoxy;
- R5 is methyl, carboxy (CO2H) or hydroxymethyl;
- R6 is hydrogen, or R5 and R6 taken together form a double bond;
- R7 and R8 are independently from each other methyl, carboxy, hydroxymethyl or methoxycarbonyl with the proviso that at least one of R7 and R8 is methyl;
- R9 is hydrogen, oxo or methoxy;
- R10 is hydrogen or R5 and R10 taken together are —CO—O—, —O—CO—, —CH2—O— or —O—CH2—;
- R13 is carboxy;
- with the further proviso for formula I that if R2 is hydroxy R1 is iso-propyl, even more preferred are the tricyclic diterpenes 7-oxodehydroabietic acid (III), totarol (IV), hydroxytotarol (V), totarol-19-carboxylic acid methyl ester (VI), sageone (VII), 8,11,13-abietatriene-11,12,20-triol (VIII), royleanoic acid (IX), ferruginol (X), carnosic acid 12-methylether (XI), most preferred are sageone (VII), 8,11,13-abietatriene-11,12,20-triol (VIII) carnosic acid 12-methylether (XI) and/or 7-methylrosmanol (XII), in particular carnosic acid 12-methylether (XI).
- The structures of the compounds (III) to (XII) are listed in table 1.
-
TABLE I tricyclic diterpenes 7-Oxodehydroabietic acid (III) (CAS 18684-55-4) Totarol (IV) 16-Hydroxytotarol (V) (CAS 2288-33-7) Totarol-19-carboxylic acid methyl ester (VI) (Methyl 13-hydroxy-14- isopropyl-9(11),12,14(8)- podocarpatrienoate) (CAS 24035-62-9) Sageone (VII) (CAS 142546-15-4) 8,11,13-abietatriene- 11,12,20-triol (VIII) Royleanoic acid (IX) Ferruginol (X) (CAS 514-62-5) Carnosic acid 12- methylether (XI) 7-Methylrosmanol (XII) - In all embodiments of the invention the term “tricyclic diterpene of formulae I and/or II” also encompasses any material or extract of a plant containing at least one tricyclic diterpene of formulae I and II in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract. The terms “material of a plant” and “plant material” used in the context of the present invention mean any part of a plant.
- “Carnosic acid 12-methyl ether” means the racemic mixture as well as pure (4aR,10aS)-carnosic acid 12-methyl ether or pure (4aS,10aR)-carnosic acid 12-methyl ether or any mixture or diastereoisomer of them. Carnosic acid 12-methyl ether can be isolated from plants like sage, rosemary, Hyptis martiusii, but not limited to it. Therefore, any material or extract of these plants or any other plant material or extract containing carnosic acid 12-methyl ether in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “Carnosic acid 12-methyl ether” means both “natural” (isolated) and “synthetic” (manufactured) carnosic acid 12-methyl ether.
- “7-oxodehydroabietic acid” means the racemic mixture as well as pure (1S,4aS,10aR)-7-oxodehydroabietic acid or pure (1R,4aR,10aS)-7-7-oxodehydroabietic acid or any mixture or diastereoisomer of them. 7-oxodehydroabietic acid can be isolated from plants like the following, but not limited to Cynara cardunculus ssp. cardunculus and Juniperus chinensis. Therefore, any material or extract of these plants or any other plant material or extract containing 7-oxodehydroabietic acid in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “7-oxodehydroabietic acid” means both “natural” (isolated) and “synthetic” (manufactured) 7-oxodehydroabietic acid.
- “Totarol” means the racemic mixture as well as pure (4bS,8aS)-totarol ((+)-totarol, trans-totarol) or pure (4bR,8aR)-totarol or any mixture or diastereoisomer of them. Totarol can be isolated from plants like the following, but not limited to sage, juniper and podocarpus sp. Therefore, any material or extract of these plants or any other plant material or extract containing totarol in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “Totarol” means both “natural” (isolated) and “synthetic” (manufactured) totarol. Totarol's synthesis is described in several articles, i.e. in Tetrahedron Letters 2003, 44(49), 8831-8835.
- “16-Hydroxytotarol” means the racemic mixture as well as pure (1S,4aS,10aR)-16-hydroxytotarol or pure (1R,4aR,10aS)-16-hydroxytotarol or any mixture or diastereoisomer of them. 16-Hydroxytotarol can be isolated from the wood of Podocarpus species and other plants. Therefore, any material or extract of these plants or any other plant material or extract containing 16-hydroxytotarol in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “16-Hydroxytotarol” means both “natural” (isolated) and “synthetic” (manufactured) 16-hydroxytotarol. 16-Hydroxytotarol's synthesis is described in several articles, i.e. in Journal of the Chemical Society, Abstracts 1963, 1553-1560 and in Chemistry & Industry (London, United Kingdom) 1963, 44, 1760-1761.
- “Totarol-19-carboxylic acid methyl ester” means the racemic mixture as well as pure (4aR,10aS)-totarol-19-carboxylic acid methyl ester or pure (4aR,10aS)-totarol-19-carboxylic acid methyl ester or any mixture or diastereoisomer of them. Totarol-19-carboxylic acid methyl ester can be isolated from the wood of Podocarpus species and other plants. Therefore, any material or extract of these plants or any other plant material or extract containing totarol-19-carboxylic acid methyl ester in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “Totarol-19-carboxylic acid methyl ester” means both “natural” (isolated) and “synthetic” (manufactured) totarol-19-carboxylic acid methyl ester. Totarol-19-carboxylic acid methyl ester can be prepared according to the process described in Chemistry & Industry (London, United Kingdom) 1963, 44, 1760-1761.
- Sageone can be isolated from plants like the following, but not limited to sage, and other salivia sp. Therefore, any material or extract of these plants or any other plant material or extract containing sageone in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “Sageone” means both “natural” (isolated) and “synthetic” (manufactured) sageone. Sageone's synthesis is described e.g. in Journal of Organic Chemistry 1997, 62(20), 6928-6951.
- “8,11,13-Abietatriene-11,12,20-triol” means the racemic mixture as well as pure (4bR,8aS)-8,11,13-abietatriene-11,12,20-triol or pure (4bS,8aR)-8,11,13-abietatriene-11,12,20-triol or any diastereoisomer or mixture of them. 8,11,13-Abietatriene-11,12,20-triol can be isolated from plants like Salivia sp. Without being limited thereto. Therefore, any material or extract of these plants or any other plant material or extract containing 8,11,13-abietatriene-11,12,20-triol in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “8,11,13-Abietatriene-11,12,20-triol” means both “natural” (isolated) and “synthetic” (manufactured) 8,11,13-abietatriene-11,12,20-triol.
- “Royleanonic acid” means the racemic mixture as well as pure (4aR,10aS)-royleanonic acid or pure (4aS,10aR)-royleanonic acid or any diastereoisomer or mixture of them. Royleanonic acid can be isolated from plants like sage (Salvia sp.), but not limited to it. Therefore, any material or extract of these plants or any other plant material or extract containing royleanonic acid in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “Royleanonic acid” means both “natural” (isolated) and “synthetic” (manufactured) royleanonic acid.
- “Ferruginol” means pure (4bS,8aS)-ferruginol or pure (4bR,8aR)-ferruginol or any stereoisomer or mixture of them. Ferruginol can be isolated from plants like Cryptomeria sp., Juniperus sp., Salvia sp., but not limited to it. Therefore, any material or extract of these plants or any other plant material or extract containing ferruginol in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, is also encompassed by this expression. “Ferruginol” means both “natural” (isolated) and “synthetic” (manufactured) ferruginol. Ferruginol's synthesis is described in Organic Letters 2001, 3(11), 1737-1740.
- Beside the (pure) compounds carnosic acid 12-methyl ether, 7-oxocallitrisic acid, totarol, 16-hydroxytotarol, totarol-19-carboxylic acid methyl ester, 20-deoxo-camosol, 7-methylrosmanol, sageone, 8,11,13-abietatriene-11,12,20-triol, royleanonic acid and ferruginol especially preferred are plant materials and plant extracts containing at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably at least 90 weight-% (i.e. from 90 to 100 weight-%), of these compounds, based on the total weight of the plant material/extract.
- In the context of this invention “treatment” also encompasses co-treatment as well as prevention. “Prevention” can be the prevention of the first occurrence (primary prevention) or the prevention of a reoccurence (secondary prevention). In the context of this invention the term “disorder” also encompasses diseases.
- The dosage and ratios of the at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and preferences as given above to an animal including humans may vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired which can be determined by the expert in the field with normal trials, or with the usual considerations regarding the formulation of a nutraceutical. A suitable daily dosage of at least one tricyclic diterpene of formulae I and/or II, with the definitions of R1 to R13 and the preferences as given above for humans may be within the range of from 0.001 mg per kg body weight to about 40 mg per kg body weight per day. More preferred is a daily dosage of from about 0.01 to about 10 mg per kg body weight, and especially preferred is a daily dosage of from about 0.05 to 5.0 mg per kg body weight. The amount of a plant material or plant extract containing such tricyclic diterpene of formulae I and II with the definitions of R1 to R13 and the preferences as given above can be calculated accordingly. In solid dosage unit preparations for humans, the tricyclic diterpene of formulae I and/or II, with the definitions of R1 to R13 and the preferences as given above, is suitably present in an amount in the range of from about 0.1 mg to about 1000 mg, preferably in the range of from about 1 mg to about 500 mg per dosage unit.
- In a different aspect, the invention also relates to tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences and definitions as given above for use as a medicament/composition for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or for the treatment, co-treatment or prevention of joint disorders.
- In another aspect, the invention relates to a nutraceutical comprising at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above and a nutraceutically acceptable carrier. In particular the invention relates to a nutraceutical comprising at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above and a nutraceutically acceptable carrier for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders.
- Also, the invention relates to a method for treatment, co-treatment and prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders in animals including humans said method comprising the step of administering an effective amount of at least one tricyclic diterpenes of formulae I and II with the definitions of R1 to R13 and the preferences as given above to animals including humans, which are in need thereof. Furthermore the invention relates to a method for the regeneration and/or maintenance of (articular) cartilage in a mammal which comprises administering to a mammal in need of such regeneration and/or maintenance an effective amount of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 as given above.
- The term ‘an effective amount’ refers to an amount necessary to obtain a physiological effect. The physiological effect may be achieved by one single dose or by repeated doses. The dosage administered may, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired and can be adjusted by a person skilled in the art.
- In the framework of the invention, with animals is meant all animals, including mammals, examples of which include humans. Preferred examples of mammals beside humans are non-ruminant or ruminant animals including cats, dogs, dromedaries, camels, elephants, and horses.
- The term nutraceutical as used herein include food product, foodstuff, dietary supplement, nutritional supplement or a supplement composition for a food product or a foodstuff.
- Thus, in another embodiment the present invention relates to a nutraceutical comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and preferences as given above in particular for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders wherein the nutraceutical is a food product, foodstuff, dietary supplement, nutritional supplement or a supplement composition for a food product or a foodstuff preferably a dietary supplement, a nutritional supplement or a supplement composition for a food or a foodstuff.
- As used herein, the term food product refers to any food or feed suitable for consumption by humans or animals. The food product may be a prepared and packaged food (e.g., mayonnaise, salad dressing, bread, or cheese food) or an animal feed (e.g., extruded and pelleted animal feed, coarse mixed feed or pet food composition). As used herein, the term foodstuff refers to any substance fit for human or animal consumption. The term dietary supplement refers to a small amount of a compound for supplementation of a human or animal diet packaged in single or multiple dose units. Dietary supplements do not generally provide significant amounts of calories but may contain other micronutrients (e.g., vitamins or minerals). The term nutritional supplement refers to a composition comprising a dietary supplement in combination with a source of calories. In some embodiments, nutritional supplements are meal replacements or supplements (e.g., nutrient or energy bars or nutrient beverages or concentrates).
- Food products or foodstuffs are for example beverages such as non-alcoholic and alcoholic drinks as well as liquid preparation to be added to drinking water and liquid food, non-alcoholic drinks are for instance soft drinks, sport drinks, fruit juices, such as for example orange juice, apple juice and grapefruit juice; lemonades, teas, near-water drinks and milk and other dairy drinks such as for example yoghurt drinks, and diet drinks. In another embodiment food products or foodstuffs refer to solid or semi-solid foods comprising the composition according to the invention. These forms can include, but are not limited to baked goods such as cakes and cookies, puddings, dairy products, confections, snack foods, or frozen confections or novelties (e.g., ice cream, milk shakes), prepared frozen meals, candy, snack products (e.g., chips), liquid food such as soups, spreads, sauces, salad dressings, prepared meat products, cheese, yogurt and any other fat or oil containing foods, and food ingredients (e.g., wheat flour).
- The term food products or foodstuffs also includes functional foods and prepared food products, the latter referring to any pre-packaged food approved for human consumption.
- Animal feed including pet food compositions advantageously include food intended to supply necessary dietary requirements, as well as treats (e.g., dog biscuits) or other food supplements. The animal feed comprising the composition according to the invention may be in the form of a dry composition (for example, kibble), semi-moist composition, wet composition, or any mixture thereof. Alternatively or additionally, the animal feed is a supplement, such as a gravy, drinking water, yogurt, powder, suspension, chew, treat (e.g., biscuits) or any other delivery form.
- Dietary supplements of the present invention may be delivered in any suitable format. In preferred embodiments, dietary supplements are formulated for oral delivery. The ingredients of the dietary supplement of this invention are contained in acceptable excipients and/or carriers for oral consumption. The actual form of the carrier, and thus, the dietary supplement itself, is not critical. The carrier may be a liquid, gel, gelcap, capsule, powder, solid tablet (coated or non-coated), tea, or the like. The dietary supplement is preferably in the form of a tablet or capsule and most preferably in the form of a hard (shell) gelatin capsule. Suitable excipient and/or carriers include maltodextrin, calcium carbonate, dicalcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid, croscarmellose sodium, sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose, methylcellulose, povidone, carboxymethylcellulose, corn starch, and the like (including mixtures thereof). Preferred carriers include calcium carbonate, magnesium stearate, maltodextrin, and mixtures thereof. The various ingredients and the excipient and/or carrier are mixed and formed into the desired form using conventional techniques. The tablet or capsule of the present invention may be coated with an enteric coating that dissolves at a pH of about 6.0 to 7.0. A suitable enteric coating that dissolves in the small intestine but not in the stomach is cellulose acetate phthalate. Further details on techniques for formulation for and administration may be found in the latest edition of Remington's Pharmaceutical Sciences (Maack Publishing Co., Easton, Pa.).
- In other embodiments, the dietary supplement is provided as a powder or liquid suitable for adding by the consumer to a food or beverage. For example, in some embodiments, the dietary supplement can be administered to an individual in the form of a powder, for instance to be used by mixing into a beverage, or by stirring into a semi-solid food such as a pudding, topping, sauce, puree, cooked cereal, or salad dressing, for instance, or by otherwise adding to a food e.g. enclosed in caps of food or beverage container for release immediately before consumption. The dietary supplement may comprise one or more inert ingredients, especially if it is desirable to limit the number of calories added to the diet by the dietary supplement. For example, the dietary supplement of the present invention may also contain optional ingredients including, for example, herbs, vitamins, minerals, enhancers, colorants, sweeteners, flavorants, inert ingredients, and the like.
- In some embodiments, the dietary supplements further comprise vitamins and minerals including, but not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; vitamin D3; cyanocobalamin; sodium selenite; copper sulfate; vitamin A; vitamin C; inositol; potassium iodide. Suitable dosages for vitamins and minerals may be obtained, for example, by consulting the U.S. RDA guidelines.
- In other embodiments, the present invention provides nutritional supplements (e.g., energy bars or meal replacement bars or beverages) comprising the composition according to the invention. The nutritional supplement may serve as meal or snack replacement and generally provides nutrient calories. Preferably, the nutritional supplements provide carbohydrates, proteins, and fats in balanced amounts. The nutritional supplement can further comprise carbohydrate, simple, medium chain length, or polysaccharides, or a combination thereof. A simple sugar can be chosen for desirable organoleptic properties. Uncooked cornstarch is one example of a complex carbohydrate. If it is desired that it should maintain its high molecular weight structure, it should be included only in food formulations or portions thereof which are not cooked or heat processed since the heat will break down the complex carbohydrate into simple carbohydrates, wherein simple carbohydrates are mono- or disaccharides. The nutritional supplement contains, in one embodiment, combinations of sources of carbohydrate of three levels of chain length (simple, medium and complex; e.g., sucrose, maltodextrins, and uncooked cornstarch).
- Sources of protein to be incorporated into the nutritional supplement of the invention can be any suitable protein utilized in nutritional formulations and can include whey protein, whey protein concentrate, whey powder, egg, soy flour, soy milk, soy protein, soy protein isolate, caseinate (e.g., sodium caseinate, sodium calcium caseinate, calcium caseinate, potassium caseinate), animal and vegetable protein and hydrolysates or mixtures thereof. When choosing a protein source, the biological value of the protein should be considered first, with the highest biological values being found in caseinate, whey, lactalbumin, egg albumin and whole egg proteins. In a preferred embodiment, the protein is a combination of whey protein concentrate and calcium caseinate. These proteins have high biological value; that is, they have a high proportion of the essential amino acids. See Modern Nutrition in Health and Disease, eighth edition, Lea & Febiger, publishers, 1986, especially Volume 1, pages 30-32. The nutritional supplement can also contain other ingredients, such as one or a combination of other vitamins, minerals, antioxidants, fiber and other dietary supplements (e.g., protein, amino acids, choline, lecithin, omega-3 fatty acids). Selection of one or several of these ingredients is a matter of formulation, design, consumer preference and end-user. The amounts of these ingredients added to the dietary supplements of this invention are readily known to the skilled artisan. Guidance to such amounts can be provided by the U.S. RDA doses for children and adults. Further vitamins and minerals that can be added include, but are not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; vitamin D3; cyanocobalamin; sodium selenite; copper sulfate; vitamin A; vitamin C; inositol; potassium iodide.
- The nutritional supplement can be provided in a variety of forms, and by a variety of production methods. In a preferred embodiment, to manufacture a food bar, the liquid ingredients are cooked; the dry ingredients are added with the liquid ingredients in a mixer and mixed until the dough phase is reached; the dough is put into an extruder, and extruded; the extruded dough is cut into appropriate lengths; and the product is cooled. The bars may contain other nutrients and fillers to enhance taste, in addition to the ingredients specifically listed herein.
- It is understood by those of skill in the art that other ingredients can be added to those described herein, for example, fillers, emulsifiers, preservatives, etc. for the processing or manufacture of a nutritional supplement.
- Additionally, flavors, coloring agents, spices, nuts and the like may be incorporated into the nutraceutical composition. Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings, peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring. Examples of useful flavoring include, but are not limited to, pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, walnut oil, cherry oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch or toffee. In one embodiment, the dietary supplement contains cocoa or chocolate.
- Emulsifiers may be added for stability of the nutraceutical. Examples of suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), and/or mono- and di-glycerides. Other emulsifiers are readily apparent to the skilled artisan and selection of suitable emulsifier(s) will depend, in part, upon the formulation and final product. Preservatives may also be added to the nutritional supplement to extend product shelf life. Preferably, preservatives such as potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate or calcium disodium EDTA are used.
- In addition to the carbohydrates described above, the nutraceutical can contain natural or artificial (preferably low calorie) sweeteners, e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol. Such artificial sweeteners can be desirable if the nutritional supplement is intended to be consumed by an overweight or obese individual, or an individual with type II diabetes who is prone to hyperglycemia.
- Moreover, a multi-vitamin and mineral supplement may be added to the nutraceuticals of the present invention to obtain an adequate amount of an essential nutrient, which is missing in some diets. The multi-vitamin and mineral supplement may also be useful for disease prevention and protection against nutritional losses and deficiencies due to lifestyle patterns.
- The dosage and ratios of the at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and preferences as given above administered via a nutraceutical will, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired which can be determined by the expert in the field with normal trials, or with the usual considerations regarding the formulation of a nutraceutical.
- A nutraceutical according to the invention may comprise at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above in an amount of about 0.001 mg to 1 g, preferably in an amount from 0.01 mg to 1 g, most preferably in the range of 2.0 mg to 300 mg per serving.
- In dietary compositions, especially in food and beverages for humans, the at least one tricyclic diterpene of formulae I and/or II, with the definitions of R1 to R13 and the preferences as given above, is suitably present in an amount in the range of from about 0.0001 (1 mg/kg) to about 5 weight-% (50 g/kg), preferably from about 0.001% (10 mg/kg) to about 1 weight-%, (10 g/kg) more preferably from about 0.01 (100 mg/kg) to about 0.5 weight-% (5 g/kg), based upon the total weight of the food or beverage.
- In food and drinks in a preferred embodiment of the invention the amount of the tricyclic diterpene of formulae I and/or II, with the definitions of R1 to R13 and the preferences as given above is in the range of from 10 to 30 mg per serving, i.e. 120 mg per kg food or drink.
- For animals excluding humans a suitable daily dosage of a tricyclic diterpene of formulae I and/or II, with the definitions of R1 to R13 and the preferences as given above, for the purposes of the present invention may be within the range of from 0.001 mg per kg body weight to about 1000 mg per kg body weight per day. More preferred is a daily dosage in the range of from about 0.1 mg to about 500 mg per kg body weight, and especially preferred is a daily dosage in the range of from about 1 mg to 100 mg per kg body weight.
- If instead of the pure compounds a plant material or plant extract comprising at least one tricyclic diterpene of formulae I and II with the definitions of R1 to R13 and the preferences as given above the dosages to be applied can be calculated accordingly.
- In another aspect, the invention relates to a pharmaceutical comprising the at least one tricyclic diterpene of formulae I and II with the definitions of R1 to R13 and preferences as given above and a pharmaceutically acceptable. In particular invention relates to a pharmaceutical comprising the at least one tricyclic diterpene of formulae I and II with the definitions of R1 to R13 and preferences as given above and a pharmaceutically acceptable the carrier for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or joint disorders.
- A person skilled in the art knows which carriers can be used as pharmaceutically acceptable carriers. Suitable pharmaceutical carriers are e.g. described in Remington's Pharmaceutical Sciences, supra, a standard reference text in this field. Examples of such pharmaceutically acceptable carriers are both inorganic and organic carrier materials, suitable for oral/parenteral/injectable administration and include water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, and the like.
- The pharmaceutical may further comprise conventional pharmaceutical additives and adjuvants, excipients or diluents, including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
- In a preferred embodiment the pharmaceutical is in the form of a powder, tablet, capsule, gel, liquid or solid embodiment.
- The dosages and ratios of the individual components in a pharmaceutical can be determined by the expert in the field with normal preclinical and clinical trials, or with the usual considerations regarding the formulation of pharmaceutical composition.
- The pharmaceutical may comprise the at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and preferences as given above in an amount from preferably 1 mg to 2000 mg per dosage unit, e.g., per capsule or tablet, or from 1 mg per daily dose to 3000 mg per daily dose of a liquid formulation. In a preferred embodiment at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and preferences as given above, preferably in the form an enriched plant extract encompassing the at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and preferences as given above in an amount of at least 30 weight-% is administered via a pharmaceutical composition either in the form of a single dose or by multiple doses in an amount of at least 0.01 mg/kg bodyweight/day, preferably in an amount of 0.1-50 mg/kg body weight/day, most preferably in an amount of 0.3-15 mg/kg body weight/day. If instead of the pure compounds a plant material or plant extract comprising at least one tricyclic diterpene of formulae I and II with the definitions of R1 to R13 and the preferences as given above the dosages to be applied can be calculated accordingly.
- The nutraceuticals and pharmaceuticals according to the present invention may be in any galenic form that is suitable for administering to the animal body including the human body, more in particular in any form that is conventional for oral administration, e.g. in solid form, for example as (additives/supplements for) food or feed, food or feed premixes, fortified food or feed, tablets, pills, granules, dragées, capsules, and effervescent formulations such as powders and tablets, or in liquid form, for instance in the form of solutions, emulsions or suspensions, for example as beverages, pastes and oily suspensions. The pastes may be filled into hard or soft shell capsules. Examples for other application forms are forms for transdermal, parenteral, topical or injectable administration. The nutraceutical and pharmaceutical compositions may be in the form of controlled (delayed) release formulations. Examples of pharmaceutical compositions also include compositions suitable for topical application and transdermal absorption of the phenolic compound, such as crèmes, gels, sprays, dry sticks, powders etc.
- Moreover, a multi-vitamin and mineral supplement may be added to the nutraceuticals or pharmaceuticals of the present invention to obtain an adequate amount of an essential nutrient, which is missing in some diets. The multi-vitamin and mineral supplement may also be useful for disease prevention and protection against nutritional losses and deficiencies due to lifestyle patterns.
- A person skilled in the art knows which carriers can be used as pharmaceutically acceptable carriers. Examples of such pharmaceutically acceptable carriers are both inorganic and organic carrier materials, suitable for oral/parenteral/injectable administration and include water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, and the like.
- Besides the at least one tricyclic diterpene of formulae I and II and a pharmaceutically acceptable carrier, the pharmaceutical composition according to the present invention, may further comprise conventional pharmaceutical additives and adjuvants, excipients or diluents, including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum Arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
- The at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and preferences as given above may be used in combination with other nutraceutical compositions or therapeutic agents known to those skilled in the art for treatment or prevention of inflammatory disorder and 7 or joint disorders by administration prior to, simultaneously with or following the administration of the at least one tricyclic diterpene of formulae I and/or II with the definitions of R1 to R13 and preferences as given above.
- According to the present invention not only the tricyclic diterpenes of the formulae I and II themselves, with the definitions of R1 to R13 and the preferences as given above, but also plant materials and extracts containing them in an amount of at least 30 weight-% (i.e. from 30 to 100 weight-%), preferably in an amount of at least 50 weight-% (i.e. from 50 to 100 weight-%), more preferably in an amount of at least 70 weight-% (i.e. from 70 to 100 weight-%), most preferably in an amount of at least 90 weight-% (i.e. from 90 to 100 weight-%), based on the total weight of the plant material or extract, as well as dietary and pharmaceutical compositions containing them can be used as medicament, especially for the treatment, co-treatment or prevention of inflammatory disorders such as arthritis, in particular of osteoarthritis and rheumatoid arthritis and/or for the treatment, co-treatment or prevention of joint disorders
- The tricyclic diterpenes or their derivatives of the formulae I and/or II with the definitions of R1 to R13 and the preferences as given above as well as (mixtures of) plant materials and plant extracts containing them (especially in an amount of at least 30 weight-%, preferably in an amount of at least 50 weight-%, more preferably in an amount of from 70 to 90 weight-%, most preferably in an amount of at least 90 weight-%, based on the total weight of the plant material or extract), and dietary/pharmaceutical compositions containing them are thus suitable for the treatment of animals including humans.
- In yet another aspect the invention also relates to the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory disorders of the skin such as sunburn, impure skin such as acne or the results of chronic skin inflammation such as photoageing. The composition comprising the at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory disorders of the skin such as sunburn, impure skin such as acne or the results of chronic skin inflammation such as photoageing may be designed for oral delivery such as a nutraceutical or a medicament or may be for topical application such as a cream or lotion without being limited hereto.
- In another aspect, the invention relates to a cosmetic or dermatological preparation (the latter preparation are a specific type of a pharmaceutical) comprising an effective amount of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above or compositions containing them (plant materials/extracts containing them in an amount of at least 30 weight-%, preferably in an amount of at least 50 weight-%, more preferably in an amount of from 70 to 90 weight-%, most preferably in an amount of at least 90 weight-%, based on the total weight of the plant material or extract; dietary/pharmaceutical compositions) and a cosmetically or dermatologically acceptable carrier.
- The cosmetic or dermatological composition may further comprise conventional cosmetic respectively dermatological adjuvants and/or additives and/or additional active ingredients.
- Preferably the cosmetic or dermatological preparations are skin care formulations for the treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn caused by UV-radiation, of contact dermatitis (particularly diaper area dermatitis), atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, thermal burns, photoageing or for the treatment, co-treatment or prevention of impure skin such as acne. Examples of impure skin include pimples, acne and other skin impurities with an inflammatory aspect.
- In yet another aspect the invention also relates to a composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory skin conditions. The composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory skin conditions may be designed for oral administration such as e.g. a nutraceutical or a pharmaceutical or a medicament or may be designed for topical application such as a cream or lotion without being limited hereto. If the composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory conditions of the skin is intended for oral administration it may be in the form of a nutraceutical or a pharmaceutical with all the definitions and preferences as given above. Such products are also known as beauty foods and supplements. If the composition comprising at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for the treatment, co-treatment or prevention of inflammatory conditions of the skin is intended for topical application it may be in the form of a cosmetic or dermatological preparation as described herein.
- The term ‘inflammatory skin conditions’ encompasses inflammatory diseases of the skin such as e.g. contact dermatitis [particularly diaper area dermatitis], atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, acne, thermal and radiation burns such as sunburn as well as any other types of skin inflammation such as e.g. photoageing which is a result of chronic skin inflammation. The term ‘inflammatory skin conditions’ also encompasses the term ‘Impure skin’. “Impure skin’ can be caused by various factors: skin irritation through various exogenous and endogenous stimuli (e.g. sun, wind, cold, dryness, incompatibility or sensitivity to crèmes, or other skin care products, overproduction of sebum consequently leading to pimples, black spots and acne). It is generally accepted that inflammatory processes in the epidermis are involved in the processes leading to skin irritation, sensitive skin and impure skin. It is furthermore well established, that in these mechanisms cytokines play an important role. Pro-inflammatory cytokines are released from keratinocytes in the epidermis upon inflammatory stimuli (Boniface K, Lecron J C, Bernard F X, Dagregorio G, Guillet G, Nau F, Morel F. Keratinocytes as targets for interleukin-10-related cytokines: a putative role in the pathogenesis of psoriasis, Eur. Cytokine Netw. 2005 December; 16(4):309-19).
- Accordingly, reduction of the response of skin cells to inflammatory stimuli can lead to an improvement of an impure or sensitive skin condition and may help to produce a pure skin with healthy and natural radiance and glow.
- Thus, the invention also relates to the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for promoting an optimal health, natural radiance and glow and/or a beautiful look of the skin. Furthermore, the invention encompasses the use of at least one tricyclic diterpenes of formulae I and/or II with the definitions of R1 to R13 and the preferences as given above for supporting a clear, pure appearance of the skin.
- The term “effective amount” means preferably at least 0.001% of each active agents based on the total weight of the cosmetic or dermatological composition. Preferably, the cosmetic or dermatological preparations comprise the active agents selected from the list above in an amount between 0.01 wt.-% and 20 wt.-%, more preferably between 0.05 and 10 wt.-%, still more preferably between 0.1 and 5 wt.-%.
- The amount of the cosmetic or dermatological preparation which is to be applied to the skin depends on the concentration of the active ingredients in the preparation and the desired cosmetic or pharmaceutical effect. For example, the application can be such that a crème is applied to the skin. A crème is usually applied in an amount of about 1 to 2 mg crème/cm2 skin. The amount of the composition which is applied to the skin is, however, not critical, and if with a certain amount of applied composition the desired effect cannot be achieved, a higher concentration of the active preparations which contain more active ingredient might be employed.
- The invention also relates to the use of the cosmetic preparation for the cosmetic treatment, co-treatment or prevention of inflammation of the skin, in particular for the cosmetic treatment, co-treatment or prevention of sunburn, contact dermatitis (particularly diaper area dermatitis), atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, thermal burns or photoageing as well as of sensitive skin towards environmental stressors (such as wind, soaps, dry climate).
- Also, the invention relates to a method for the treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn in humans, of impure skin such as for example acne or of photoageing which is associated with chronic skin inflammation, said method comprising the step of administering an effective amount of the dermatological composition according to the invention to humans, which are in need thereof. Also, the invention relates to a method for cosmetic treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn or of impure skin such as acne by a cosmetic preparation according to the invention. Sunburn prevention is preferably achieved with topical application comprising the composition of the invention preferably in combination with suitable light screening agents.
- The cosmetic or dermatological preparations according to the invention may be in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of O/W or W/O type, O/W/O or W/O/W-type, wherein O stands for oil phase and wherein W stands for water phase), such as a cream, a paste, a lotion, a thickened lotion or a milk, a vesicular dispersion in the form of an ointment, a gel, a solid tube stick or an aerosol mousse, and may be provided in the form of a mousse, foam or a spray foams, sprays, sticks or aerosols or wipes. Examples of cosmetic or dermatological preparations are skin care preparations, in particular, body oils, body lotions, body gels, treatment creams, skin protection ointments, moisturizing gels, moisturizing sprays, revitalizing body sprays, after sun preparations or sunscreen formulations.
- The cosmetic or dermatological composition for the treatment, co-treatment or prevention of inflammation of the skin, such as for example sunburn, photoageing or impure skin may be in a form that is conventional for oral administration, examples of which are described above and also include beauty foods and supplements.
- The cosmetic or dermatological preparations of the invention for instance as sunscreen formulations or after sun preparations may further comprise the usual cosmetic respectively dermatological adjuvants and/or additives such as preservatives/antioxidants, fatty substances/oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, additional light screening agents, antifoaming agents, moisturizers, fragrances, surfactants, fillers, sequestering agents, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorants, pigments or nanopigments, light stabilizers, insect repellants, skin tanning agents, skin whitening agents, antibacterial agents, preservatives active ingredients or any other ingredients usually formulated into cosmetics.
- Light screening agents which may be incorporated into cosmetic or dermatological preparations of the invention for instance sunscreen formulations are advantageously selected from IR, UV-A, UV-B, UV-C and/or broadband filters. Examples of UV-B or broad spectrum screening agents, i.e. substances having absorption maxima between about 290 and 340 nm may be organic or inorganic compounds. Organic UV-B or broadband screening agents are e.g. acrylates such as 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (octocrylene, PARSOL® 340), ethyl 2-cyano-3,3-diphenylacrylate and the like; camphor derivatives such as 4-methyl benzylidene camphor (PARSOL® 5000), 3-benzylidene camphor, camphor benzalkonium methosulfate, polyacrylamidomethyl benzylidene camphor, sulfo benzylidene camphor, sulphomethyl benzylidene camphor, therephthalidene dicamphor sulfonic acid and the like; Cinnamate derivatives such as ethylhexyl methoxycinnamate (PARSOL® MCX), ethoxyethyl methoxycinnamate, diethanolamine methoxycinnamate (PARSOL® Hydro), isoamyl methoxycinnamate and the like as well as cinnamic acid derivatives bond to siloxanes; p-aminobenzoic acid derivatives, such as p-aminobenzoic acid, 2-ethylhexyl p-dimethylaminobenzoate, N-oxypropylenated ethyl p-aminobenzoate, glyceryl p-aminobenzoate; benzophenones such as benzophenone-3, benzophenone-4,2,2′,4,4′-tetrahydroxy-benzophenone, 2,2′-dihydroxy-4,4′-dimethoxybenzophenone and the like; esters of benzalmalonic acid such as di-(2-ethylhexyl) 4-methoxybenzalmalonate; esters of 2-(4-ethoxy-anilinomethylene)propandioic acid such as 2-(4-ethoxy anilinomethylene)propandioic acid diethyl ester as described in the European Patent Publication EP 0895 776; organosiloxane compounds containing benzmalonate groups as described in the European Patent Publications EP 0358584 B1, EP 0538431 B1 and EP 0709080 A1 such as polysilicone-15 (PARSOL® SLX); drometrizole trisiloxane (Mexoryl XL); imidazole derivatives such as e.g. 2-phenyl benzimidazole sulfonic acid and its salts (PARSOL®HS). Salts of 2-phenyl benzimidazole sulfonic acid are e.g. alkali salts such as sodium- or potassium salts, ammonium salts, morpholine salts, salts of primary, sec. and tert. amines like monoethanol amine salts, diethanol amine salts and the like; salicylate derivatives such as isopropylbenzyl salicylate, benzyl salicylate, butyl salicylate, ethylhexyl salicylate (PARSOL® EHS, NEO Heliopan OS), isooctyl salicylate or homomethyl salicylate (homosalate, PARSOL® HMS, NEO Heliopan OS) and the like; triazine derivatives such as ethylhexyl triazone (Uvinul T-150), diethylhexyl butamido triazone (Uvasorb HEB). Encapsulated UV-filters such as encapsulated ethylhexyl methoxycinnamate (Eusolex UV-pearls) or microcapsules loaded with UV-filters as e.g. disclosed in EP 1471995 and the like. Inorganic compounds are pigments such as microparticulated TiO2, ZnO and the like. The term “microparticulated” refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm. The TiO2 particles may also be coated by metal oxides such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art.
- Examples of broad spectrum or UV A screening agents i.e. substances having absorption maxima between about 320 and 400 nm may be organic or inorganic compounds e.g. dibenzoylmethane derivatives such as 4-tert. butyl-4′-methoxydibenzoyl-methane (PARSOL® 1789), dimethoxydibenzoylmethane, isopropyldibenzoylmethane and the like; benzotriazole derivatives such as 2,2′-methylene-bis-(6-(2H-benzotriazole-2-yl)-4-(1,1,3,3,-tetramethylbutyl)-phenol (TINOSORB M) and the like; bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S) and the like; phenylene-1,4-bis-benzimidazolsulfonic acids or salts such as 2,2-(1,4-phenylene)bis-(1H-benzimidazol-4,6-disulfonic acid) (Neoheliopan AP); amino substituted hydroxybenzophenones such as 2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoic acid hexylester (Uvinul A plus) as described in the European Patent Publication EP 1046391; Ionic UV-A filters as described in the International Patent Publication WO2005080341 A1. Pigments such as microparticulated ZnO or TiO2 and the like. The term “microparticulated” refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm. The particles may also be coated by other metal oxides such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art.
- As dibenzoylmethane derivatives have limited photostability, it may be desirable to photostabilize these UV-A screening agents. Thus, the term “conventional UV-A screening agent” also refers to dibenzoylmethane derivatives such as e.g. PARSOL® 1789 stabilized by, e.g. 3,3-Diphenylacrylate derivatives as described in the European Patent Publications EP 0 514 491 B1 and EP 0 780 119 A1; Benzylidene camphor derivatives as described in the U.S. Pat. No. 5,605,680; Organosiloxanes containing benzmalonate groups as described in the European Patent Publications EP 0358584 B1, EP 0538431 B1 and EP 0709080 A1.
- Active ingredients which may be included in the cosmetic or dermatological preparations of the invention are for example vitamins and derivatives thereof, for example tocopherol, tocopherol acetate, ascorbic acid, ascorbyl phosphate, vitamin Q, D, and K, retinol, retinal, retinoic acid, retinol acetate, retinol palmitate, biotin, carotenoid derivatives such as beta-carotene, lycopene, astaxanthin, vegetable extracts, antibacterial ingredients, instable amino acids comprising dipeptides, oligopeptides and polypeptides such as methionine, cysteine, cystine, tryptophan, phenylalanine, tyrosine, phenols, polyphenols or flavanoids, bisabolol, allantoin, phytantriol, panthenol, AHA acids, ubiquinones such as coenzyme Q 10, ceramides, pseudoceramides, essential oils, plant extracts deoxyribonucleic acid, phytanic acid.
- The necessary amounts of the cosmetic and dermatological adjuvants, additives and/or additional active ingredients can, based on the desired product, easily be chosen by a person skilled in the art and will be illustrated in the examples, without being limited hereto.
- The invention will now be elucidated by way of the following examples, without however being limited thereto.
- The Sageone (VII) and 8,11,13-Abietatriene-11,12,20-triol (in the following referred to Abietatrienetriol) (VIII) were obtained from Analyticon, carnosic acid 12-methylether (XI) was isolated from a lipophilic extract of rosemary needles by chromatography in a purity >95%.
- The anti-inflammatory effects of carnosic acid-12-methyl ether, sageone and abietatrientriol were evaluated in activated macrophages by determining the inhibition of the synthesis of nitric oxide and/or proinflammatory prostaglandins (PG). PGE2 plays a critical role in the inflammation process, while nitric oxide (NO) is a hallmark of inflammation in various chronic inflammatory diseases including various forms of arthritis, gastro-intestinal diseases and metabolic syndrome.
- The compounds were dissolved in DMSO in concentrated form and did not contain byproducts that interfered with the assays. Final vehicle (DMSO) concentration did not exceed 0.2% v/v in the assays.
- The anti-inflammatory effects of compounds was tested in cellular assays using a murine macrophage indicator cell line, RAW267.7, which was purchased from American Type Culture Collection, (ATCC) and cultured in DMEM according to the protocol provided by ATCC. Cells (˜50'000/well) were seeded into flat-bottomed microtiter plates and cultured for one day. Cells were then starved in complete medium containing 0.25% fetal calf serum (FCS) (D-025). After overnight culture, medium was removed and replaced by 100 μL of D-025 containing the test compounds at twice the final concentration. Subsequently, 100 μL of D-025 containing 2 μg/ml lipopolysaccharide (LPS) was added (i.e. final LPS concentration of 1 μg/ml) and the cells were cultured for 24 hours. Substances were usually tested in a concentration range from 0.2 to 50 μM in two-fold dilution steps. Concentrations of nitrite which was generated from nitric oxide released by cells were determined by the Griess reaction (see e.g Imai et al. Biochem Biophys Res Comm, 197, 105 [1993]) using sodium nitrite as standard. Briefly, 50 μl of supernatant was mixed with Griess reagent 1 (25 μL) and Griess reagent 2 (25 μL), centrifuged and the optical density at 540 nm determined. PGE2 secreted into the cell culture medium was determined by EIA obtained from Cayman Chemicals (Ann Harbor, Wis., USA) and used according to the manufacturer's instructions. IC50 values were calculated using a two-parametric least-square fitting equation [y=A+((B−A)/(1+((C−x)̂D))] for best-fit curves (Excel fit software program).
- In Table 2 it is shown that all substances idiosyncratically inhibited the production of inflammatory mediators. This is indicated by IC50 values, which vary between substances reflecting substance-specific biological potencies.
-
TABLE 2 IC50 values for single substances Substance IC50 PGE2 IC50 Nitric Oxide Sageone (VII) 16.9 ± 0.8 μmol/L 7.3 ± 2.1 μmol/L Abietatriene triol (IX) 7.8 ± 4.6 μmol/L 12.5 ± 4.8 μmol/L Carnosic acid-12-methyl 44.4 ± 6.1 μmol/L 3.8 ± 0.6 μmol/L ether (XII) - In articular cartilage, a delicate balance between anabolic (build-up) and catabolic (break down) events needs to be maintained in order to prevent hypertrophy and excessive degradation of extracellular matrix (ECM), respectively. The ECM is built up of collagen and proteoglycans that are the products of collagen genes, for example human collagen I or aggrecan genes, which are activated and expressed during anabolic processes.
- Catabolic events are controlled by the expression of genes, for example those genes that encode matrix metalloproteinases (MMPs) that eventually break down collagen or proteoglycans. Of the MMPs, MMP-1, MMP-3 and MMP-13 have a major role in decomposing the ECM in cartilage degradation.
- The cells were treated with IL-1β, which is one of the natural mediators that induce cartilage breakdown and is detected in substantial amounts in osteoarthritic cartilage tissues and cells derived thereof. Treatment of cells with IL-1β triggers the expression of genes that are involved in catabolic events, such as MMPs. Also, treatment of the cells with IL-1β reduces the collagen expression levels (compared to untreated cells)
- Chondrocytes (SW1353; purchased from the American Tissue Culture Collection [ATCC]) were grown in cell culture medium according to the instructions from ATCC. For experimental treatments, cells were seeded into 6-well plates and cultured for two days until they reached confluence. Total cellular RNA was extracted from cultured cells and reverse-transcribed as described by Richard et al. Mol. Nutr. Food Res. 49, 431-442, 2005. Expression levels of distinct genes were determined by quantitative real-time PCR as described in Richard et al. Mol. Nutr. Food Res. 49, 431-442, 2005. Results of this experiment are shown in Table 2 below:
-
TABLE 3 Effect of compounds on gene expression in human chondrocyte cells. Percentages indicate gene expressionlevels relative to cells that were treated without the compound. 12.5 μM Carnosic 0 μM 12.5 μM acid 12-methyl 12.5 μM Gene compound Abietatrienetriol ether Sageone Human 100% 30% 94% 3% MMP-1 Human 100% Not done 69% 112% MMP-3 Human 100% 49% 60% 36% MMP-13 Human 100% 257% Not done 120% collagen I Human 100% 295% 139% — collagen II Aggrecan 100% 264% 123% 152% - Compounds drastically reduced the expression of genes involved in the degradation of cartilage (MMP-1, MMP-3 and MMP-13), whereas they stimulated the expression of some genes associated with the build-up of cartilage (human collagen I, human collagen II, aggrecan). These results suggest that the indicated compounds not only prevent degradation of cartilage, but also help to regenerate cartilage tissue.
- Soft gelatin capsules are prepared by conventional procedures providing a dose of Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) of 10 mg. A suitable daily dose is 1 to 5 capsules.
- Other ingredients: glycerol. Water, gelatine, vegetable oil
- Hard gelatin capsules are prepared by conventional procedures providing a dose of Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) of 20 mg. A suitable daily dose is 1 to 5 capsules.
- Other ingredients:
Fillers: lactose or cellulose or cellulose derivatives q.s.
Lubricant: magnesium stearate if necessary (0.5%) - Tablets are prepared by conventional procedures providing as active ingredient 20 mg of Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) per tablet, and as excipients microcrystalline cellulose, silicone dioxide (SiO2), magnesium stearate, crospovidone NF (which is a disintegration agent) ad 500 mg.
- A soft drink containing a Tricyclic diterpene of formulae I and/or II such as carnosic acid 12-methylether (XI) may be prepared as follows:
- A soft drink is prepared from the following ingredients:
-
ingredient [g] A. juice concentrates and water soluble flavours 60.3°Brix, 5.15% acidity 657.99 43.5° Brix, 32.7% acidity 95.96 Orange flavour, water soluble 3.43 Apricot flavour, water soluble 6.71 water 26.46 B. color β-carotene 10% CWS 0.89 water 67.65 C. Acid and antioxidant Ascorbic acid 4.11 Citric acid anhydrous 0.69 water 43.18 D. stabilizers pectin 0.20 Sodium benzoate 2.74 water 65.60 E. oil soluble flavours Orange flavour, oil soluble 0.34 Orange oil distilled 0.34 F. active ingredient Tricyclic diterpene of formulae I and/or II Amount providing 500 mg such as carnosic acid 12-methylether (XI) - Fruit juice concentrates and water soluble flavours are mixed without incorporation of air. The color is dissolved in deionized water. Ascorbic acid and citric acid are dissolved in water. Sodium benzoate is dissolved in water. The pectin is added under stirring and dissolved while boiling. The solution is cooled down. Orange oil and oil soluble flavours are premixed. The active ingredient as mentioned under F is stirred into the fruit juice concentrate mixture of A.
- In order to prepare the soft drinks all components A-F are mixed together before homogenizing using a Turrax and then a high-pressure homogenizer (p1=200 bar, p2=50 bar).
- Commercial dry dog food (Hill's Science diet “Canine Maintenance dry” for dogs as supplied by Hill's Pet Nutrition GmbH, Liebigstrasse 2-20, D-22113) is sprayed with an aqueous ROPUFA (as supplied by DSM Nutritional Products) in an amount sufficient to administer to a subject a daily dose of 4 mg to 120 mg ROPUFA per kg body weight. Further L-ascorbic acid-monophosphate (ROVIMIX® STAY-C® 35 from DSM Nutritional Products AG, Vitamin E and beta-carotene and carnosic acid-12-methylether are incorporated in an amount sufficient to provide 30 mg ROVIMIX® STAY-C® 35/kg, and 300 IU vitamin E/kg and 280 mg beta-carotene/kg and 100 mg of carnosic acid-12-methylether in the final food composition before extruding the entire blend. The food composition is dried to contain dry matter of about 90% by weight.
- Commercial wet cat food (Hill's Science diet “Feline Maintenance wet” for cats as supplied by Hill's Pet Nutrition GmbH, Liebigstrasse 2-20, D-22113) is mixed with an aqueous dispersion of ROPUFA (as supplied by DSM Nutritional Products) in an amount sufficient to administer to a subject a daily dose of 4 mg to 120 mg ROPUFA. Further L-ascorbic acid-monophosphate (ROVIMIX® STAY-C® 35 from DSM Nutritional Products AG, Vitamin E and beta-carotene and sageone are incorporated in an amount sufficient to provide 30 mg ROVIMIX® STAY-C® 35 kg, and 300 IU vitamin E/kg and 280 mg beta-carotene/kg and 200 mg/kg of sageone in the final food composition before cooking the entire blend. The food composition is dried to contain a dry matter of about 90% by weight.
- A treatment cream may be prepared with the following ingredients, in the following amounts:
-
Ingredients INCI Nomenclature % w/w A Glyceryl Myristate Glyceryl Myristate 2.00 Tricyclic diterpene of formulae e.g. carnosic acid 0.05-25 I and/or II 12-methylether (XI) Cetyl Alcohol Cetyl Alcohol 0.50 Myritol 318 Caprylic/Capric 5.00 Triglyceride Crodamol DA Diisopropyl Adipate 5.00 Vitamin E acetate Tocopheryl Acetate 2.00 Butylated Hydroxytoluene BHT 0.05 Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethyl-paraben & Propylparaben & Butylparaben Edeta BD Disodium EDTA 0.10 AMPHISOL K Potassium Cetyl 2.00 Phosphate B Water deionized Aqua ad 100 1,2-Propylene Glycol Propylene Glycol 2.00 D-PANTHENOL 75 L Panthenol 2.00 Ethanol Ethanol 5.00 Allantoin Allantoin 0.20 Carbopol ETD 2001 Carbomer 0.30 C KOH 10% sol. Potassium Hydroxide 1.50 D Perfume Perfume q.s. Procedure: Heat part A) and B) to 85° C. while stirring. When homogeneous, add part B) to A) under agitation. Cool to about 45° C. while stirring. Add part C). Homogenize at 11000 rpm to achieve a small particle size. Cool to ambient temperature while stirring. Then add part D). -
-
Ingredients INCI Nomenclature % w/w A) PARSOL SLX Polysilicone-15 6.00 Neo Heliopan AP 3.00 Tinosorb S Hydrogenated Cocoglycerides 3.00 Lanette O Cetearyl Alcohol 2.00 Myritol 318 Caprylic/capric Triglyceride 6.00 Mineral oil Mineral oil 2.00 Vitamin E acetate Tocopheryl Acetate 1.00 Prisorine 3515 Isostearyl Alcohol 4.00 B) Edeta BD Disodium EDTA 0.10 Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben Amphisol K Potassium Cetyl Phosphate 2.00 Water deionized Aqua ad100 1,2-Propylene Glycol Propylene Glycol 5.00 Carbopol 981 Carbomer 0.30 Tinosorb M Methylene Bis-Benzotriazolyl 6.00 Tetramethylbutylphenol KOH 10% solution Potassium Hydroxyde 2.10 C) Tricyclic diterpene of e.g. sageone (VII)) 0.05-2 formulae I and/or II Procedure: Heat part A) and B) to 85° C. while stirring. When homogeneous, add part B) to A) under agitation. Cool to ambient temperature while stirring and add part C). Homogenize to achieve a small particle size. -
-
Ingredients INCI Nomenclature % w/w A) PARSOL SLX Polysilicone-15 6.00 PARSOL 1789 Butyl 2.00 Methoxydibenzoylmethane PARSOL 5000 4-Methylbenzylidene Camphor 4.00 Uvinul T 150 Ethylhexyltriazone 2.00 Silicone DC 200/350 cs Dimethicone 1.00 Lanette O Cetearyl Alcohol 2.00 Softisan 100 Hydrogenated Coco-Glycerides 3.00 Tegosoft TN C12-15 Alkyl Benzoate 6.00 Cetiol B Dibutyl Adipate 7.00 Vitamin E acetate Tocopheryl Acetate 2.00 BHT BHT 0.05 Edeta BD Disodium EDTA 0.10 Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben Amphisol Cetyl Phosphate DEA 2.00 B) Water deionized Aqua ad 100 Propylene Glycol Propylene Glycol 5.00 Carbopol 980 Carbomer 0.30 KOH (10% sol.) Potassium Hydroxide 1.50 C) Tricyclic diterpene of e.g. carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI) Procedure: Heat part A) and B) to 85° C. while stirring. When homogeneous, add part B) to A) under agitation. Cool to ambient temperature while stirring and add part C). Homogenize to achieve a small particle size. -
-
Ingredients INCI Nomenclature % w/w A) Tegosoft TN C12-15 Alkyl Benzoate 5.00 Silicone 2503 Cosmetic Stearyl Dimethicone 2.00 Wax Cetyl Alcohol Cetyl Alcohol 1.00 Butylated BHT 0.05 Hydroxytoluene Estol GMM 3650 Glyceryl Myristate 4.00 Edeta BD Disodium EDTA 0.10 Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben Amphisol A Cetyl Phosphate 2.00 B) Water deionized Aqua ad 100 Carbopol 980 Carbomer 0.6 Glycerine Glycerine 3.00 KOH sol. 10% Potassium Hydroxide 2.4 C) Tricyclic diterpene of e.g. carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI) Procedure: Heat part A) and B) to 85° C. while stirring. When homogeneous, add part B) to A) under agitation. Cool to ambient temperature while stirring and add part C). Homogenize to achieve a small particle size. -
-
Ingredients INCI Nomenclature % w/w A) PARSOL SLX Polysilicone-15 6.00 PARSOL 1789 Butyl 2.00 Methoxydibenzoylmethane PARSOL 5000 4-Methylbenzylidene Camphor 4.00 Uvinul T 150 2.00 Silicone DC 200/350 cs Dimethicone 1.00 Lanette O Cetearyl Alcohol 2.00 Softisan 100 Hydrogenated Coco-Glycerides 3.00 Tegosoft TN C12-15 Alkyl Benzoate 6.00 Cetiol B Dibutyl Adipate 7.00 Vitamin E acetate Tocopheryl Acetate 2.00 BHT BHT 0.05 Edeta BD Disodium EDTA 0.10 Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben Amphisol K Potassium Cetyl Phosphate 2.00 B) Water deionized Aqua ad 100 Propylene Glycol Propylene Glycol 5.00 Carbopol 980 Carbomer 0.30 KOH (10% sol.) Potassium Hydroxide 1.50 C) Tricyclic diterpene of e.g. sageone (VII)) 0.05-5 formulae I and/or II D) Perfume Perfume q.s. Procedure: Heat part A) and B) to 85° C. while stirring. When homogeneous, add part B) to A) under agitation. Cool to ambient temperature while stirring and add part C) and D). Homogenize to achieve a small particle size. -
-
Ingredients INCI Nomenclature % w/w A) PARSOL MCX Ethylhexyl Methoxycinnamate 6.00 PARSOL 1789 Butyl Methoxydibenzoylmethane 4.00 PARSOL 5000 4-Methylbenzylidene Camphor 4.00 Uvasorb HEB Diethylhexyl Butamido Triazone 1.50 Uvinul A plus 2.00 Vitamin E acetate Tocopheryl Acetate 1.50 Tegosoft TN C12-15 Alkyl Benzoate 9.00 Elefac I-205 Ethylhexyldodecyl Neopentanoate 2.00 Alcohol Alcohol ad 100 Isopropyl Alcohol Isopropyl Alcohol 20.00 B) Klucel MF Hydroxypropylcellulose 2.00 C) Tricyclic diterpene of For example carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI) D) perfume q.s. Procedure: Mix part A) and B) while stirring. When homogeneous, add part C) and D) under agitation. -
-
Ingredients INCI Nomenclature % w/w A) Pemulen TR-2 Acrylates/C10-30 Alky 0.60 Acrylate Crosspolymer Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben Edeta BD Disodium EDTA 0.1 Aqua Aqua ad 100 B) PARSOL 1789 Butyl 4.00 Methoxydibenzoylmethane PARSOL 340 Octocrylene 3.00 Tegosoft TN C12-15 Alkyl Benzoate 15.00 Antaron V-216 PVP/Hexadecene Copolymer 1.00 Vitamin E acetate Tocopheryl Acetate 0.50 Butylated Hydroxytoluene BHT 0.05 Cremophor RH 410 PEG-40 Hydrogenated Castor 0.50 Oil Tris Amino Tromethamine 0.50 C) Tricyclic diterpene of For example carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI) D) Perfume Perfume q.s. Procedure: Heat part A) and B) to 85° C. while stirring. When homogeneous, add part B) to A) under agitation. Cool to ambient temperature while stirring and add part C) and D). Homogenize to achieve a small particle size. -
-
Ingredients INCI Nomenclature % w/w A) PARSOL 1789 Butyl 2.00 Methoxydibenzoylmethane PARSOL 5000 4-Methylbenzylidene 4.00 Camphor Uvinul T 150 Ethylhexyl Triazone 2.00 Uvinul TiO2 Titanium Dioxide and 5.00 Trimethoxycaprylylsilane Arlacel P 135 PEG-30 2.00 Dipolyhydroxystearate Tegosoft TN C12-15 Alkyl Benzoate 5.00 Cosmacol EMI Di-C12-13 Alkyl Malate 6.00 Miglyol 840 Propylene Glycol Dicaprylate/ 6.00 Dicaprate Butylated Hydroxytoluene BHT 0.05 Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben B) Deionized water Aqua ad 100 Glycerin Glycerin 5.00 Edeta Disodium EDTA 0.1 NaCl Sodium Chloride 0.30 C) PARSOL HS Phenylbenzyimidazole 4.00 Sulphonic Acid Water Aqua 20.00 Triethanolamine 99%. Triethanolamine 2.50 D) Tricyclic diterpene of For example carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI) E) Perfume q.s. Procedure: Heat part A), B) and C) to 85° C. while stirring. When homogeneous, add part B) and C) to A) under agitation. Cool to ambient temperature while stirring and add part D) and E). Homogenize to achieve a small particle size. -
-
Ingredients INCI Nomenclature % w/w A) Cremophor WO 7 PEG-7 Hydrogenated Castor Oil 6.00 Elfacos ST 9 PEG-45/Dodecyl Glycol 2.00 Copolymer PARSOL 1789 Butyl 3.00 Methoxydibenzoylmethane Tinosorb S 5.00 PARSOL 5000 4-Methylbenzylidene Camphor 4.00 microfine ZnO Zinc Oxide 2.00 Microcrystalline wax Microcrystalline Wax 2.00 Miglyol 812 Caprylic/capric Triglyceride 5.00 Vitamin E acetate Tocopheryl Acetate 1.00 Jojoba oil Simmondsia Chinensis Seed Oil 5.00 Edeta BD Disodium EDTA 0.10 Butylated BHT 0.05 Hydroxytoluene Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben B) Water deionized Aqua ad 100 Glycerin Glycerin 5.00 C) Neo Heliopan AP 2.00 Water deionized Aqua 20.00 KOH 10% solution Potassium Hydroxide 4.00 D) Tricyclic diterpene of For example carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI) E) Perfume Perfume q.s. Procedure: Heat part A), B) and C) to 85° C. while stirring. When homogeneous, add part B) and C) to A) under agitation. Cool to ambient temperature while stirring and add part D) and E). Homogenize to achieve a small particle size. -
-
Ingredients INCI Nomenclature % w/w A) PARSOL SLX Polysilicone-15 4.00 PARSOL 1789 Butyl 1.50 Methoxydibenzoylmethane Glyceryl Myristate Glyceryl Myristate 2.00 Cetyl Alcohol Cetyl Alcohol 0.50 Myritol 318 Caprylic/Capric Triglyceride 5.00 Crodamol DA Diisopropyl Adipate 5.00 Vitamin E acetate Tocopheryl Acetate 2.00 Butylated BHT 0.05 Hydroxytoluene Phenonip Phenoxyethanol & 0.60 Methylparaben & Ethylparaben & Propylparaben & Butylparaben Edeta BD Disodium EDTA 0.10 Amphisol K Potassium Cetyl Phosphate 2.00 B) Water deionized Aqua ad 100 1,2-Propylene Glycol Propylene Glycol 2.00 D-Panthenol 75 L Panthenol 2.00 Ethanol Ethanol 5.00 Allantoin Allantoin 0.20 Carbopol ETD 2001 Carbomer 0.30 KOH 10% sol. Potassium Hydroxide 1.50 C) Water Aqua 10.00 Stay-C 50 Sodium Ascorbyl Phosphate 0.50 D) Tricyclic diterpene of For example carnosic acid 0.05-25 formulae I and/or II 12-methylether (XI) E) Perfume Perfume q.s.
Claims (19)
1. Use of at least one tricyclic diterpene of formulae I and/or II
wherein R1 is hydrogen or C1-6-alkyl;
R2 is hydroxy, C3-5-acyloxy, hydroxymethyl, 1,3-dihydroxypropyl or C1-6-alkyl;
R3 and R4 are independently from each other hydrogen, hydroxy, hydroxymethyl (—CH2—OH), C1-5-acyloxy or C1-6-alkoxy;
R5 is C1-6-alkyl, hydroxymethyl, carboxy (CO2H) or methoxycarbonyl (CO2CH3);
R6 is hydrogen, or R5 and R6 taken together form a double bond;
R7 and R8 are independently from each other C1-6-alkyl, carboxy, x-hydroxy-Cx-alkyl (with x being an integer from 1 to 6), or C1-6-alkoxycarbonyl (—CO2(C1-6-alkyl)) with the proviso that at least one of R7 and R8 is C1-6-alkyl;
R9 is hydrogen, hydroxymethyl, methoxy, oxo or C1-5-acyloxy;
R10 is hydrogen or R5 and R10 taken together are —CO—O—, —O—CO—, —CH2—O—or —O—CH2—;
R11 and R12 are both hydrogen or R11 and R12 together are oxo;
R13 is C1-6-alkyl, hydroxymethyl, carboxy (CO2H) or methoxycarbonyl (CO2CH3) or R6 and R13 taken together form a double bond
with the further proviso for formula I that if R2 is hydroxy R1 is C1-6-alkyl for the manufacture of a nutraceutical or pharmaceutical for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
2. The use according to claim 1 , wherein the at least one tricyclic diterpene is a compound of formulae I and/or II wherein R1 is hydrogen or iso-propyl; R2 is hydroxy or iso-propyl; R3 and R4 are independently from each other hydrogen, hydroxy or methoxy; R5 is methyl, carboxy (CO2H) or hydroxymethyl; R6 is hydrogen, or R5 and R6 taken together form a double bond; R7 and R8 are independently from each other methyl, carboxy, hydroxymethyl or methoxycarbonyl with the proviso that at least one of R7 and R8 is methyl; R9 is hydrogen, oxo or methoxy; R10 is hydrogen or R5 and R10 taken together are —CO—O—, —O—CO—, —CH2—O— or —CH2—; R13 is carboxy with the further proviso for formula I that if R2 is hydroxy R1 is iso-propyl.
3. The use according to claim 1 wherein the at least one tricyclic diterpene of formulae I and/or II is 7-oxodehydroabietic acid, totarol, hydroxytotarol, totarol-19-carboxylic acid methyl ester, sageone, 8,11,13-abietatriene-11,12,20-triol, royleanoic acid, ferruginol, carnosic acid 12-methylether and/or 7-methylrosmanol.
4. The use according to claim 1 , wherein the at least one tricyclic diterpene of formulae I and/or II is comprised in a plant extract in an amount of at least 30 weight-%.
5. The use according to claim 1 , wherein the inflammatory disorder is arthritis.
6. A nutraceutical comprising at least one tricyclic diterpene of formulae I and/or II as defined in claim 1 and a nutraceutically acceptable carrier for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
7. The nutraceutical according to claim 6 which is a food product, foodstuff, dietary supplement, nutritional supplement or a supplement composition for a food product or a foodstuff.
8. The nutraceutical according to claims 6 in which the amount of the at least one tricyclic diterpene of formulae I and/or II is in the range of 0.01 mg to 1000 mg, preferably in the range of 2.0 mg to 300 mg per serving.
9. A pharmaceutical comprising at least one tricyclic diterpene of formulae I and/or II as defined in claim 1 and a pharmaceutically acceptable carrier for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
10. A cosmetic or dermatological composition comprising at least one tricyclic diterpene of formulae I and/or II as defined in claim 1 and a cosmetically acceptable carrier.
11. The cosmetic composition or dermatological according to claim 10 which is a skin care preparation.
12. The cosmetic or dermatological composition according to claim 10 for the treatment, co-treatment or prevention of sunburn and/or impure skin.
13. The tricyclic diterpene of formulae I and/or II as defined in claim 1 for use as a medicament for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders.
14. Use of at least one tricyclic diterpene of formulae I and/or II as defined in claim 1 for the treatment, co-treatment or prevention of inflammatory disorders of the skin such as sunburn, impure skin or the results of chronic skin inflammation such as photoageing.
15. Use of at least one tricyclic diterpene of formulae I and/or II as defined in claim 1 for the treatment, co-treatment or prevention of cartilage degradation or cartilage damage in joints, for cartilage regeneration or cartilage maintenance, or for maintenance of joint health.
16. A method for treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders in animals including humans said method comprising the step of administering an effective amount of at least one tricyclic diterpene of formulae I and/or II according to claim 1 to animals including humans, which are in need thereof.
17. Method according to claim 16 , wherein the inflammatory disorder is arthritis.
18. Method according to claim 16 , wherein the inflammatory disorder is inflammation of the skin, in particular sunburn or impure skin.
19. The method according to claim 16 wherein the at least one tricyclic diterpene of formulae I and/or II as defined in any one of claims 1 - to 3 are comprised in a plant extract in an amount of at least 30 weight-%.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06024382.1 | 2006-11-24 | ||
EP06024382A EP1925301A1 (en) | 2006-11-24 | 2006-11-24 | Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders |
PCT/EP2007/010071 WO2008061720A2 (en) | 2006-11-24 | 2007-11-21 | Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders |
Publications (1)
Publication Number | Publication Date |
---|---|
US20100056615A1 true US20100056615A1 (en) | 2010-03-04 |
Family
ID=37708418
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/515,329 Abandoned US20100056615A1 (en) | 2006-11-24 | 2007-11-21 | Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders |
US12/515,332 Expired - Fee Related US8680147B2 (en) | 2006-11-24 | 2007-11-21 | Compositions |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/515,332 Expired - Fee Related US8680147B2 (en) | 2006-11-24 | 2007-11-21 | Compositions |
Country Status (6)
Country | Link |
---|---|
US (2) | US20100056615A1 (en) |
EP (3) | EP1925301A1 (en) |
JP (4) | JP5517124B2 (en) |
KR (2) | KR101526611B1 (en) |
CN (2) | CN101594859B (en) |
WO (2) | WO2008061724A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014137231A3 (en) * | 2013-03-07 | 2014-12-31 | T2G Biotechnology Limited | Totarol extract formulations and uses thereof |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1925301A1 (en) * | 2006-11-24 | 2008-05-28 | DSMIP Assets B.V. | Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders |
ES2366865T3 (en) * | 2008-07-08 | 2011-10-26 | Cognis Ip Management Gmbh | METHOD FOR THE PREPARATION OF (+) - TOTAROL. |
JP5610681B2 (en) * | 2008-09-19 | 2014-10-22 | 株式会社ノエビア | Neutral fat accumulation inhibitor |
BR112013031355A2 (en) * | 2011-06-08 | 2016-09-06 | Dsm Ip Assets Bv | cosmetic compositions |
CN102532250B (en) * | 2011-11-07 | 2013-09-25 | 中国科学院昆明植物研究所 | Przewalsikone A compound with anti-tumor activity and preparation method and application thereof |
WO2013070018A1 (en) * | 2011-11-11 | 2013-05-16 | (주)아모레퍼시픽 | Composition comprising carnosic acid or derivative thereof |
US11198724B2 (en) * | 2013-03-14 | 2021-12-14 | The Regents Of The University Of Michigan | Treatment of staphylococcal disorders |
DE102013108870A1 (en) | 2013-08-16 | 2015-02-19 | Aimecs Gmbh | Agent for cleaning and protecting technical surfaces |
JP6202471B2 (en) | 2013-10-31 | 2017-09-27 | 日油株式会社 | Method for producing medical polyoxypropylene polymer and method for producing medical polyoxypropylene / polyoxyethylene block copolymer |
CN105017155B (en) * | 2014-04-16 | 2017-06-16 | 华东师范大学 | Class tricyclic diterpene and pyrazole derivatives and its preparation method and application |
JP6170231B1 (en) * | 2016-12-22 | 2017-07-26 | 株式会社タイショーテクノス | DYE PREPARATION AND ITS MANUFACTURING METHOD, AND PROCESSED PRODUCT AND ITS MANUFACTURING METHOD |
PL236429B1 (en) * | 2017-07-06 | 2021-01-11 | Emergopharm Spolka Z Ograniczona Odpowiedzialnoscia Spolka Komandytowa | Application of totarol and the totarol-containing pharmaceutical composition |
CN107823196A (en) * | 2017-11-24 | 2018-03-23 | 广西医科大学 | Application of the carnosic acid in terms for the treatment of medicine for treating rheumatoid arthritis is prepared |
WO2021178351A1 (en) * | 2020-03-02 | 2021-09-10 | University Of South Florida | Tricyclic diterpene isolated from pine rosin for the treatment of pain and inflammation |
US20210315930A1 (en) * | 2020-04-14 | 2021-10-14 | David A. Cuddeback | Nutraceutical composition for multimodal prophylaxis against and treatment of viral and bacterial infection and inflammation |
CN111686020A (en) * | 2020-06-23 | 2020-09-22 | 中南大学 | Application of carnosic acid in preparation of anti-photoaging product |
CN112707795B (en) * | 2020-12-31 | 2022-04-01 | 中南大学 | Preparation method of Icetexane type abietane diterpene |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4942033A (en) * | 1983-12-27 | 1990-07-17 | L'oreal | Vegetable extract-based cosmetic or pharmaceutical composition which acts on capillary brittleness |
US5256700A (en) * | 1990-10-06 | 1993-10-26 | Nestec S.A. | Carnosic acid obtention and uses |
US20020114849A1 (en) * | 2001-02-16 | 2002-08-22 | Camper Jurdon Wayne | Therapeutic body lotion containing alkali metal hypohalite |
US20020176876A1 (en) * | 2001-01-23 | 2002-11-28 | Harris Dennis H. | Topical therapeutic skin care system |
US6492429B1 (en) * | 2000-07-10 | 2002-12-10 | N.V. Nutricia | Composition for the treatment of osteoarthritis |
US6638523B1 (en) * | 1999-10-27 | 2003-10-28 | Nagase & Company, Ltd. | Method of treating ulcers |
US20040247706A1 (en) * | 2003-06-06 | 2004-12-09 | Roberts Stephen C. | Transdermal dietary supplement comprising parthenolide |
US20050073154A1 (en) * | 2003-09-11 | 2005-04-07 | Maurice Dudley | Underwater electric generator |
US6881857B2 (en) * | 1999-05-14 | 2005-04-19 | Nereus Pharmaceuticals, Inc. | Tricyclic diterpene derivatives |
WO2005073154A1 (en) * | 2004-01-28 | 2005-08-11 | Douglas Anthony Mende | A method of extracting totarol and/or a product containing totarol |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2700071B2 (en) * | 1988-06-10 | 1998-01-19 | 株式会社資生堂 | Antimicrobial agent, skin external preparation and oral composition using the same |
JPH11318387A (en) * | 1989-10-31 | 1999-11-24 | Kanebo Ltd | Food product for anti-inflammation |
US5358752A (en) * | 1993-02-23 | 1994-10-25 | Norac Technologies Inc. | Skin care composition |
FR2707496B1 (en) * | 1993-06-30 | 1995-09-22 | Dolisos Lab | Antiradical and / or antilipoperoxidative and / or hepatotropic pharmaceutical compositions. |
JPH09194385A (en) * | 1996-01-10 | 1997-07-29 | Ichimaru Pharcos Co Ltd | Antiallergic agent and preparation for external use for skin or bathing agent blended with the same agent |
JPH1036282A (en) * | 1996-07-18 | 1998-02-10 | Pola Chem Ind Inc | Agent for suppressing breakage of mucopolysaccharide |
US6387416B1 (en) | 2001-04-05 | 2002-05-14 | Thomas Newmark | Anti-Inflammatory herbal composition and method of use |
KR20040015145A (en) * | 2001-04-25 | 2004-02-18 | 다나베 세이야꾸 가부시키가이샤 | Potassium Channel Opener |
US6831101B2 (en) * | 2001-06-14 | 2004-12-14 | Chemokine Therapeutics Corporation | Tricyclic rantes receptor ligands |
ATE421877T1 (en) * | 2001-09-17 | 2009-02-15 | Johnson & Johnson Consumer | USE OF TOTAROL TO TREAT PRURITUS |
JP3766009B2 (en) * | 2001-09-28 | 2006-04-12 | 江崎グリコ株式会社 | Curry powder having high antioxidant property and excellent flavor, and food containing the curry powder |
JP2005015440A (en) * | 2003-06-27 | 2005-01-20 | Herb Road Co | Antilipidemic agent and food or beverage containing the same |
WO2005025586A1 (en) | 2003-09-12 | 2005-03-24 | Access Business Group International Llc | Cytokine modulators and related method of use |
KR200371655Y1 (en) * | 2004-10-12 | 2005-01-03 | 이흥우 | A silencer for vehicle |
JP2006124363A (en) * | 2004-10-28 | 2006-05-18 | Noboru Tagami | Anticonvulsant and health food, food and drink containing the same |
CA2629529A1 (en) | 2004-11-18 | 2006-05-26 | Biopharmacopae Design International Inc. | Plant extracts and dermatological uses thereof |
JP4934280B2 (en) * | 2005-02-07 | 2012-05-16 | 花王株式会社 | Wrinkle improving agent |
EP1925301A1 (en) * | 2006-11-24 | 2008-05-28 | DSMIP Assets B.V. | Use of tricyclic diterpenes and their derivatives for the treatment, co-treatment or prevention of inflammatory disorders and/or joint disorders |
-
2006
- 2006-11-24 EP EP06024382A patent/EP1925301A1/en not_active Ceased
-
2007
- 2007-11-21 WO PCT/EP2007/010076 patent/WO2008061724A2/en active Application Filing
- 2007-11-21 US US12/515,329 patent/US20100056615A1/en not_active Abandoned
- 2007-11-21 CN CN200780050450XA patent/CN101594859B/en not_active Expired - Fee Related
- 2007-11-21 KR KR1020097013051A patent/KR101526611B1/en not_active IP Right Cessation
- 2007-11-21 WO PCT/EP2007/010071 patent/WO2008061720A2/en active Application Filing
- 2007-11-21 CN CNA2007800503865A patent/CN101600420A/en active Pending
- 2007-11-21 EP EP07846706A patent/EP2083805A2/en not_active Withdrawn
- 2007-11-21 JP JP2009537529A patent/JP5517124B2/en not_active Expired - Fee Related
- 2007-11-21 US US12/515,332 patent/US8680147B2/en not_active Expired - Fee Related
- 2007-11-21 JP JP2009537532A patent/JP5487520B2/en not_active Expired - Fee Related
- 2007-11-21 KR KR1020097013050A patent/KR101550073B1/en not_active IP Right Cessation
- 2007-11-21 EP EP07846710A patent/EP2083810A2/en not_active Withdrawn
-
2013
- 2013-06-26 JP JP2013134253A patent/JP5633855B2/en not_active Expired - Fee Related
- 2013-06-26 JP JP2013134254A patent/JP5633856B2/en not_active Expired - Fee Related
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4942033A (en) * | 1983-12-27 | 1990-07-17 | L'oreal | Vegetable extract-based cosmetic or pharmaceutical composition which acts on capillary brittleness |
US5256700A (en) * | 1990-10-06 | 1993-10-26 | Nestec S.A. | Carnosic acid obtention and uses |
US6881857B2 (en) * | 1999-05-14 | 2005-04-19 | Nereus Pharmaceuticals, Inc. | Tricyclic diterpene derivatives |
US6638523B1 (en) * | 1999-10-27 | 2003-10-28 | Nagase & Company, Ltd. | Method of treating ulcers |
US6492429B1 (en) * | 2000-07-10 | 2002-12-10 | N.V. Nutricia | Composition for the treatment of osteoarthritis |
US20020176876A1 (en) * | 2001-01-23 | 2002-11-28 | Harris Dennis H. | Topical therapeutic skin care system |
US20020114849A1 (en) * | 2001-02-16 | 2002-08-22 | Camper Jurdon Wayne | Therapeutic body lotion containing alkali metal hypohalite |
US20040247706A1 (en) * | 2003-06-06 | 2004-12-09 | Roberts Stephen C. | Transdermal dietary supplement comprising parthenolide |
US20050073154A1 (en) * | 2003-09-11 | 2005-04-07 | Maurice Dudley | Underwater electric generator |
WO2005073154A1 (en) * | 2004-01-28 | 2005-08-11 | Douglas Anthony Mende | A method of extracting totarol and/or a product containing totarol |
Non-Patent Citations (1)
Title |
---|
Darmati et al. "Natural terpenoids isolated from the grown variety of sage" J. Serb. Chem.Soc., 1993, vol. 58, no. 7-8, pp. 515-523. * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014137231A3 (en) * | 2013-03-07 | 2014-12-31 | T2G Biotechnology Limited | Totarol extract formulations and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
WO2008061724A2 (en) | 2008-05-29 |
JP2010510267A (en) | 2010-04-02 |
JP5633856B2 (en) | 2014-12-03 |
US20100056634A1 (en) | 2010-03-04 |
KR20090083478A (en) | 2009-08-03 |
WO2008061724A3 (en) | 2008-08-21 |
WO2008061720A3 (en) | 2008-10-23 |
EP1925301A1 (en) | 2008-05-28 |
JP2013227328A (en) | 2013-11-07 |
JP5517124B2 (en) | 2014-06-11 |
JP2010510266A (en) | 2010-04-02 |
WO2008061720A2 (en) | 2008-05-29 |
CN101594859B (en) | 2012-08-08 |
JP5633855B2 (en) | 2014-12-03 |
KR101526611B1 (en) | 2015-06-05 |
EP2083810A2 (en) | 2009-08-05 |
EP2083805A2 (en) | 2009-08-05 |
KR101550073B1 (en) | 2015-09-03 |
JP2013255495A (en) | 2013-12-26 |
CN101594859A (en) | 2009-12-02 |
KR20090089883A (en) | 2009-08-24 |
CN101600420A (en) | 2009-12-09 |
US8680147B2 (en) | 2014-03-25 |
JP5487520B2 (en) | 2014-05-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8680147B2 (en) | Compositions | |
US8841264B2 (en) | Compositions | |
US20100055218A1 (en) | Novel compositions | |
US20090186942A1 (en) | Novel nutraceutical and pharmaceutical compositions and use thereof for the treatment, co-treatment or prevention of inflammatory disorders | |
WO2008006582A1 (en) | Compositions comprising magnolol or honokiol and other active agents for the treatment of inflammatory diseases | |
US20140162976A1 (en) | Compositions comprising hydroxytyrosol and chondroitin and use thereof for the treatment, co-treatment or prevention of inflammatory disorders | |
US20110300240A1 (en) | Cajanus extracts and glucosamine for inflammatory disorders | |
US8158681B2 (en) | Nutraceutical and pharmaceutical compositions and use thereof for the treatment, co-treatment or prevention of inflammatory disorders | |
US20090149420A1 (en) | Novel compositions and use thereof for the treatment, co-treatment or prevention of inflammatory disorders | |
US20090156666A1 (en) | Novel compositions and use thereof for the treatment, co-treatment or prevention of inflammatory disorders |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: DSM IP ASSETS B.V.,NETHERLANDS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:RAEDERSTORFF, DANIEL;SCHUELER, GOEDE;SCHWAGER, JOSEPH;AND OTHERS;SIGNING DATES FROM 20090512 TO 20090526;REEL/FRAME:023483/0017 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |